Exploration of Medicine

Table 3. Mechanisms of action of topical drugs for the therapy of NP for excitatory and inhibitory effects

Mechanism of action of topical agents	Receptor ion channel enzyme	Topical agent utilized in clinical practice	Possible site of action	Reference
Mechanism for excitatory effect of drugs	Voltage-gated sodium channels (NaVs)	Lidocaine, amitriptyline, doxepin, phenytoin, ambroxol, TV-45070, opioids, NSAIDs, clonidine	Neurons, keratinocytes	[128–132]
	TRPV1	Capsaicin, NSAIDs	Neurons, keratinocytes, immune cells	[133–135]
	VGCC	Gabapentin, lidocaine	Neurons, keratinocytes	[136–138]
	NMDAR	Ketamine, amitriptyline, diclofenac	Neurons, keratinocytes, immune cells	[139–141]
	COX-2	NSAIDs	Neurons, immune cells, Schwann cells	[142–144]
Mechanism for inhibitory effect of drugs	GABAR	Amitriptyline	Neurons, keratinocytes, immune cells	[145–148]
	GABA_AR	Ketamine, phenytoin	Neurons, keratinocytes, immune cells	[149, 150]
	GABA_BR	Baclofen	Neurons, keratinocytes, immune cells	[151–154]
	α₂-AR	Clonidine	Neurons	[155–157]
	OR	Opioids	Neurons, keratinocytes, immune cells	[158–160]
	CR	Cannabinoids	Neurons, keratinocytes, immune cells	[161–163]

Return to article view

α₂-AR: α₂ adreno receptors; COX-2: cyclooxygenase-2; CR: cannabinoid receptors; GABAR: γ-aminobutyric acid receptors; GABA_AR: γ-aminobutyric acid type A receptors; TV-45070: topical sodium channel inhibitor; NMDAR: NMDA receptors; NSAIDs: Non-steroidal anti-inflammatory drugs; OR: opioid receptors; TRPV1: transient receptor potential vanilloid 1

Declarations

Acknowledgments

Our sincere thanks to Paramveer Singh, Shadab Husain and Jamilur Rahman Ansari for editing the language of this manuscript. The authors gratefully acknowledge the contributions of the collaborators and co-workers mentioned in the cited reference. SC, R Kaur, and AG acknowledges K.R. Mangalam University, AW acknowledges Guru Gobind Singh Indraprastha University (GGSIPU). R Kadian gratefully acknowledges the support and cooperation from the Director of Ram Gopal College, Gurugram. MSA gratefully acknowledges the Vice Chancellor and Dean of Pharmacy, Shree Guru Gobind Singh Tricentenary University (SGTU) for their kind cooperation and support.

Author contributions

SC, AW, R Kaur, and AG: Conceptualization, Investigation, Writing—original draft, Writing—review & editing. R Kadian and MSA: Validation, Writing—review & editing, Supervision.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

Not applicable.

Copyright

References

Merskey HE. Classification of chronic pain: descriptions of chronic pain syndromes and definitions of pain terms. Pain. 1986;Suppl 3:226.

Bernetti A, Agostini F, de Sire A, Mangone M, Tognolo L, Di Cesare A, et al. Neuropathic pain and rehabilitation: a systematic review of international guidelines. Diagnostics. 2021;11:74. [DOI] [PubMed] [PMC]

Lo J, Chan L, Flynn S. A systematic review of the incidence, prevalence, costs, and activity and work limitations of amputation, osteoarthritis, rheumatoid arthritis, back pain, multiple sclerosis, spinal cord injury, stroke, and traumatic brain injury in the United States: a 2019 update. Arch Phys Med Rehabil. 2021;102:115–31. [DOI] [PubMed] [PMC]

Seddighi AS, Seddighi A, Ghadirian M, Zali A, Far SMT. Neuropathic pain: mechanism, representation, management and treatment. J Int Clin Neurosci. 2022;9:e18. [DOI]

Marchettini P, Formaglio F, Lacerenza M. Neuropathic pain. In: Eduardo Bruera IJ, Higginson CF, von Gunten TM, editor. Textbook of palliative medicine and supportive care. Boca Raton: CRC Press; 2021. pp. 301–12. [DOI]

Batmaz SB, Birinci G, Aslan EA. Quality of life of children with allergic disease: the effect of depression and anxiety of children and their mothers. J Asthma. 2022;59:1776–86. [DOI] [PubMed]

Samadi Z, Jannati Y, Hamidia A, Mohammadpour RA, Hesamzadeh A. The effect of aromatherapy with lavender essential oil on sleep quality in patients with major depression. J Nurs Midwif Sci. 2021;8:67–73. [DOI]

Merskey H, Bogduk N. Classification of chronic pain. 2nd ed. Seattle: IASP Press; 1994.

Colloca L, Ludman T, Bouhassira D, Baron R, Dickenson AH, Yarnitsky D, et al. Neuropathic pain. Nat Rev Dis Primers. 2017;3:17002. [DOI] [PubMed] [PMC]

10.

Pottoo FH, Sharma S, Javed MN, Barkat MA, Harshita, Alam MS, et al. Lipid-based nanoformulations in the treatment of neurological disorders. Drug Metab Rev. 2020;52:185–204. [DOI] [PubMed]

11.

van Hecke O, Austin SK, Khan RA, Smith BH, Torrance N. Neuropathic pain in the general population: a systematic review of epidemiological studies. Pain. 2014;155:654–62. [DOI] [PubMed]

12.

Pandey M, Saleem S, Nautiyal H, Pottoo FH, Javed MN. PINK1/Parkin in neurodegenerative disorders: crosstalk between mitochondrial stress and neurodegeneration. In: Uddin MS, Ashraf GM, editor. Quality control of cellular protein in neurodegenerative disorders. Hershey: IGI Global; 2020. [DOI]

13.

Finnerup NB, Sindrup SH, Jensen TS. The evidence for pharmacological treatment of neuropathic pain. Pain. 2010;150:573–81. [DOI] [PubMed]

14.

Finnerup NB, Attal N, Haroutounian S, McNicol E, Baron R, Dworkin RH, et al. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. Lancet Neurol. 2015;14:162–73. [DOI] [PubMed] [PMC]

15.

Fornasari D. Pharmacotherapy for neuropathic pain: a review. Pain Ther. 2017;6:25–33. [DOI] [PubMed] [PMC]

16.

Vadivelu N, Kai A, Maslin B, Kodumudi G, Legler A, Berger JM. Tapentadol extended release in the management of peripheral diabetic neuropathic pain. Ther Clin Risk Manag. 2015;11:95–105. [DOI] [PubMed] [PMC]

17.

Sanford M. Intrathecal ziconotide: a review of its use in patients with chronic pain refractory to other systemic or intrathecal analgesics. CNS Drugs. 2013;27:989–1002. [DOI] [PubMed]

18.

Pottoo FH, Tabassum N, Javed MN, Nigar S, Sharma S, Barkat MA, et al. Raloxifene potentiates the effect of fluoxetine against maximal electroshock induced seizures in mice. Eur J Pharm Sci. 2020;146:105261. [DOI] [PubMed]

19.

Field MJ, Li Z, Schwarz JB. Ca²⁺ channel α₂-δ ligands for the treatment of neuropathic pain. J Med Chem. 2007;50:2569–75. [DOI] [PubMed]

20.

Heinke B, Balzer E, Sandkühler J. Pre- and postsynaptic contributions of voltage-dependent Ca²⁺ channels to nociceptive transmission in rat spinal lamina I neurons. Eur J Neurosci. 2004;19:103–11. [DOI] [PubMed]

21.

Dolphin AC, Menon-Johansson A, Campbell V, Berrow N, Sweeney MI. GABA_B receptors and G proteins modulate voltage-dependent calcium channels in cultured rat dorsal root ganglion neurons: relevance to transmitter release and its modulation. Neurophysiology. 1994;26:29–35. [DOI]

22.

Westenbroek RE, Hoskins L, Catterall WA. Localization of Ca²⁺ channel subtypes on rat spinal motor neurons, interneurons, and nerve terminals. J Neurosci. 1998;18:6319–30. [DOI] [PubMed] [PMC]

23.

King T, Ossipov MH, Vanderah TW, Porreca F, Lai J. Is paradoxical pain induced by sustained opioid exposure an underlying mechanism of opioid antinociceptive tolerance? Neurosignals. 2005;14:194–205. [DOI] [PubMed]

24.

Yamamoto T, Nair P, Davis P, Ma SW, Navratilova E, Moye S, et al. Design, synthesis, and biological evaluation of novel bifunctional C-terminal-modified peptides for δ/μ opioid receptor agonists and neurokinin-1 receptor antagonists. J Med Chem. 2007;50:2779–86. [DOI] [PubMed] [PMC]

25.

Yamamoto T, Nair P, Jacobsen NE, Davis P, Ma SW, Navratilova E, et al. The importance of micelle-bound states for the bioactivities of bifunctional peptide derivatives for δ/μ opioid receptor agonists and neurokinin 1 receptor antagonists. J Med Chem. 2008;51:6334–47. [DOI] [PubMed] [PMC]

26.

Pottoo FH, Tabassum N, Javed MN, Nigar S, Rasheed R, Khan A, et al. The synergistic effect of raloxifene, fluoxetine, and bromocriptine protects against pilocarpine-induced status epilepticus and temporal lobe epilepsy. Mol Neurobiol. 2019;56:1233–47. [DOI] [PubMed]

27.

Siddall PJ, Cousins MJ. Spinal pain mechanisms. Spine. 1997;22:98–104. [DOI] [PubMed]

28.

Sorkin LS, Xiao WH, Wagner R, Myers RR. Tumour necrosis factor-α induces ectopic activity in nociceptive primary afferent fibres. Neuroscience. 1997;81:255–62. [DOI] [PubMed]

29.

Nicholson B. Gabapentin use in neuropathic pain syndromes. Acta Neurol Scand. 2000;101:359–71. [DOI] [PubMed]

30.

Amir R, Devor M. Chemically mediated cross-excitation in rat dorsal root ganglia. J Neurosci. 1996;16:4733–41. [DOI] [PubMed] [PMC]

31.

Patil PG, Campbell JN. Lesions of primary afferent and sympathetic efferents as treatments for pain. In: Bonica’s management of pain. 3rd ed. Baltimore: Lippincott Williams & Wilkins; 2001. pp. 2011–22.

32.

Pottoo FH, Bhowmik M, Vohora D. Raloxifene protects against seizures and neurodegeneration in a mouse model mimicking epilepsy in postmenopausal woman. Eur J Pharm Sci. 2014;65:167–73. [DOI] [PubMed]

33.

Schott GD. Visceral afferents: their contribution to ‘sympathetic dependent’ pain. Brain. 1994;117:397–413. [DOI] [PubMed]

34.

Rowbotham MC, Petersen KL. Anticonvulsants and local anesthetic drugs. In: Loeser JD, Butler S, Chapman CR, Turk DC, editor. Bonica’s management of pain. 3rd ed. Philadelphia: Williams & Wilkins; 2001. pp. 1727–35.

35.

Pasero C. Pathophysiology of neuropathic pain. Pain Manage Nurs. 2004;5:3–8. [DOI] [PubMed]

36.

Pottoo FH, Javed MN, Barkat MA, Alam MS, Nowshehri JA, Alshayban DM, et al. Estrogen and serotonin: complexity of interactions and implications for epileptic seizures and epileptogenesis. Curr Neuropharmacol. 2019;17:214–31. [DOI] [PubMed] [PMC]

37.

Kuner R, Flor H. Structural plasticity and reorganisation in chronic pain. Nat Rev Neurosci. 2017;18:20–30. Erratum in: Nat Rev Neurosci. 2017;18:158. [DOI] [PubMed]

38.

Rowbotham MC, Yosipovitch G, Connolly MK, Finlay D, Forde G, Fields HL. Cutaneous innervation density in the allodynic form of postherpetic neuralgia. Neurobiol Dis. 1996;3:205–14. [DOI] [PubMed]

39.

Ochoa JL, Campero M, Serra J, Bostock H. Hyperexcitable polymodal and insensitive nociceptors in painful human neuropathy. Muscle Nerve. 2005;32:459–72. [DOI] [PubMed]

40.

Reichling DB, Levine JD. Critical role of nociceptor plasticity in chronic pain. Trends Neurosci. 2009;32:611–8. [DOI] [PubMed] [PMC]

41.

Ratté S, Prescott SA. Afferent hyperexcitability in neuropathic pain and the inconvenient truth about its degeneracy. Curr Opin Neurobiol. 2016;36:31–7. [DOI] [PubMed]

42.

Beydoun A, Backonja MM. Mechanistic stratification of antineuralgic agents. J Pain Symptom Manage. 2003;25:S18–30. [DOI] [PubMed]

43.

Yaksh TL. Calcium channels as therapeutic targets in neuropathic pain. J Pain. 2006;7:S13–30. [DOI] [PubMed]

44.

Xiao WH, Bennett GJ. Synthetic omega-conopeptides applied to the site of nerve injury suppress neuropathic pains in rats. J Pharmacol Exp Ther. 1995;274:666–72. [PubMed]

45.

Bridges D, Thompson SW, Rice AS. Mechanisms of neuropathic pain. Br J Anaesth. 2001;87:12–26. [DOI] [PubMed]

46.

Attal N. Chronic neuropathic pain: mechanisms and treatment. Clin J Pain. 2000;16:S118–30. [DOI] [PubMed]

47.

Woolf CJ. Evidence for a central component of post-injury pain hypersensitivity. Nature. 1983;306:686–8. [DOI] [PubMed]

48.

Laird MA, Gidal BE. Use of gabapentin in the treatment of neuropathic pain. Ann Pharmacother. 2000;34:802–7. [DOI] [PubMed]

49.

Simms BA, Zamponi GW. Neuronal voltage-gated calcium channels: structure, function, and dysfunction. Neuron. 2014;82:24–45. [DOI] [PubMed]

50.

Sindrup SH, Jensen TS. Efficacy of pharmacological treatments of neuropathic pain: an update and effect related to mechanism of drug action. Pain. 1999;83:389–400. [DOI] [PubMed]

51.

Latremoliere A, Woolf CJ. Central sensitization: a generator of pain hypersensitivity by central neural plasticity. J Pain. 2009;10:895–926. [DOI] [PubMed] [PMC]

52.

Gracely RH, Lynch SA, Bennett GJ. Painful neuropathy: altered central processing maintained dynamically by peripheral input. Pain. 1992;51:175–94. [DOI] [PubMed]

53.

Loeser JD, Treede RD. The Kyoto protocol of IASP basic pain terminology. Pain. 2008;137:473–7. [DOI] [PubMed]

54.

Ibrahim AM, Pottoo FH, Dahiya ES, Khan FA, Kumar JBS. Neuron-glia interactions: molecular basis of alzheimer’s disease and applications of neuroproteomics. Eur J Neurosci. 2020;52:2931–43. [DOI] [PubMed]

55.

Truini A, Cruccu G. Pathophysiological mechanisms of neuropathic pain. Neurol Sci. 2006;27:S179–82. [DOI] [PubMed]

56.

Vaillancourt PD, Langevin HM. Painful peripheral neuropathies. Med Clin North Am. 1999;83:627–42. [DOI] [PubMed]

57.

Salter MW. Cellular signalling pathways of spinal pain neuroplasticity as targets for analgesic development. Curr Top Med Chem. 2005;5:557–67. [DOI] [PubMed]

58.

Costigan M, Scholz J, Woolf CJ. Neuropathic pain: a maladaptive response of the nervous system to damage. Annu Rev Neurosci. 2009;32:1–32. [DOI] [PubMed] [PMC]

59.

Snutch TP. Targeting chronic and neuropathic pain: the N-type calcium channel comes of age. NeuroRx. 2005;2:662–70. [DOI] [PubMed] [PMC]

60.

Heinricher MM, Tavares I, Leith JL, Lumb BM. Descending control of nociception: specificity, recruitment and plasticity. Brain Res Rev. 2009;60:214–25. [DOI] [PubMed] [PMC]

61.

Hille B, Beech DJ, Bernheim L, Mathie A, Shapiro MS, Wollmuth LP. Multiple G-protein-coupled pathways inhibit N-type Ca channels of neurons. Life Sci. 1995;56:989–92. [DOI] [PubMed]

62.

Bovill JG. Mechanisms of actions of opioids and non-steroidal anti-inflammatory drugs. Eur J Anaesthesiol. 1997;14:9–15. [DOI] [PubMed]

63.

Zamponi GW, Snutch TP. Modulation of voltage-dependent calcium channels by G proteins. Curr Opin Neurobiol. 1998;8:351–6. [DOI] [PubMed]

64.

Christie MJ, Connor M, Vaughan CW, Ingram SL, Bagley EE. Cellular actions of opioids and other analgesics: implications for synergism in pain relief. Clin Exp Pharmacol Physiol. 2000;27:520–3. [DOI] [PubMed]

65.

Schroeder CI, Lewis RJ. ω-conotoxins GVIA, MVIIA and CVID: SAR and clinical potential. Mar Drugs. 2006;4:193–214. [DOI] [PMC]

66.

Olivera BM, Gray WR, Zeikus R, McIntosh JM, Varga J, Rivier J, et al. Peptide neurotoxins from fish-hunting cone snails. Science. 1985;230:1338–43. [DOI] [PubMed]

67.

Olivera BM, Miljanich GP, Ramachandran J, Adams ME. Calcium channel diversity and neurotransmitter release: the ω-conotoxins and omega-agatoxins. Annu Rev Biochem. 1994;63:823–67. [DOI] [PubMed]

68.

Feng ZP, Doering CJ, Winkfein RJ, Beedle AM, Spafford JD, Zamponi GW. Determinants of inhibition of transiently expressed voltage-gated calcium channels by ω-conotoxins GVIA and MVIIA. J Biol Chem. 2003;278:20171–8. [DOI] [PubMed]

69.

Williams ME, Feldman DH, McCue AF, Brenner R, Velicelebi G, Ellis SB, et al. Structure and functional expression of α1, α2, and β subunits of a novel human neuronal calcium channel subtype. Neuron. 1992;8:71–84. [DOI] [PubMed]

70.

Vanegas H, Schaible H. Effects of antagonists to high-threshold calcium channels upon spinal mechanisms of pain, hyperalgesia and allodynia. Pain. 2000;85:9–18. [DOI] [PubMed]

71.

de Souza AH, Castro CJ Jr, Rigo FK, de Oliveira SM, Gomez RS, Diniz DM, et al. An evaluation of the antinociceptive effects of Phα1β, a neurotoxin from the spider Phoneutria nigriventer, and ω-conotoxin MVIIA, a cone snail Conus magus toxin, in rat model of inflammatory and neuropathic pain. Cell Mol Neurobiol. 2013;33:59–67. [DOI] [PubMed]

72.

Prado WA. Involvement of calcium in pain and antinociception. Braz J Med Biol Res. 2001;34:449–61. [DOI] [PubMed]

73.

Ellinor PT, Zhang JF, Horne WA, Tsien RW. Structural determinants of the blockade of N-type calcium channels by a peptide neurotoxin. Nature. 1994;372:272–5. [DOI] [PubMed]

74.

Vega T, De Pascual R, Bulbena O, García AG. Effects of omega-toxins on noradrenergic neurotransmission in beating guinea pig atria. Eur J Pharmacol. 1995;276:231–8. [DOI] [PubMed]

75.

Scott DA, Wright CE, Angus JA. Actions of intrathecal ω-conotoxins CVID, GVIA, MVIIA, and morphine in acute and neuropathic pain in the rat. Eur J Pharmacol. 2002;451:279–86. [DOI] [PubMed]

76.

Pin JP, Bockaert J. ω-conotoxin GVIA and dihydropyridines discriminate two types of Ca²⁺ channels involved in GABA release from striatal neurons in culture. Eur J Pharmacol. 1990;188:81–4. [DOI] [PubMed]

77.

Wang YX, Pettus M, Gao D, Phillips C, Scott Bowersox S. Effects of intrathecal administration of ziconotide, a selective neuronal N-type calcium channel blocker, on mechanical allodynia and heat hyperalgesia in a rat model of postoperative pain. Pain. 2000;84:151–8. [DOI] [PubMed]

78.

Jain KK. An evaluation of intrathecal ziconotide for the treatment of chronic pain. Expert Opin Investig Drugs. 2000;9:2403–10. [DOI] [PubMed]

79.

Wermeling DP, Berger JR. Ziconotide infusion for severe chronic pain: case series of patients with neuropathic pain. Pharmacotherapy. 2006;26:395–402. [DOI] [PubMed]

80.

Miljanich GP. Ziconotide: neuronal calcium channel blocker for treating severe chronic pain. Curr Med Chem. 2004;11:3029–40. [DOI] [PubMed]

81.

Wermeling DP. Ziconotide, an intrathecally administered N-type calcium channel antagonist for the treatment of chronic pain. Pharmacotherapy. 2005;25:1084–94. [DOI] [PubMed]

82.

Micheli L, Rajagopalan R, Lucarini E, Toti A, Parisio C, Carrino D, et al. Pain relieving and neuroprotective effects of non-opioid compound, DDD-028, in the rat model of paclitaxel-induced neuropathy. Neurotherapeutics. 2021;18:2008–20. [DOI] [PubMed] [PMC]

83.

Wang YX, Gao D, Pettus M, Phillips C, Bowersox SS. Interactions of intrathecally administered ziconotide, a selective blocker of neuronal N-type voltage-sensitive calcium channels, with morphine on nociception in rats. Pain. 2000;84:271–81. [DOI] [PubMed]

84.

Adams DJ, Smith AB, Schroeder CI, Yasuda T, Lewis RJ. Omega-conotoxin CVID inhibits a pharmacologically distinct voltage-sensitive calcium channel associated with transmitter release from preganglionic nerve terminals. J Biol Chem. 2003;278:4057–62. [DOI] [PubMed]

85.

Lewis RJ, Nielsen KJ, Craik DJ, Loughnan ML, Adams DA, Sharpe IA, et al. Novel ω-conotoxins from Conus catus discriminate among neuronal calcium channel subtypes. J Biol Chem. 2000;275:35335–44. [DOI] [PubMed]

86.

Li Q, Lu J, Zhou X, Chen X, Su D, Gu X, et al. High-voltage-activated calcium channel in the afferent pain pathway: an important target of pain therapies. Neurosci Bull. 2019;35:1073–84. [DOI] [PubMed] [PMC]

87.

Smith MT, Cabot PJ, Ross FB, Robertson AD, Lewis RJ. The novel N-type calcium channel blocker, AM336, produces potent dose-dependent antinociception after intrathecal dosing in rats and inhibits substance P release in rat spinal cord slices. Pain. 2002;96:119–27. [DOI] [PubMed]

88.

Miljanich GP, Ramachandran J. Antagonists of neuronal calcium channels: structure, function, and therapeutic implications. Annu Rev Pharmacol Toxicol. 1995;35:707–34. [DOI] [PubMed]

89.

Dolphin AC. Functions of presynaptic voltage-gated calcium channels. Function (Oxf). 2021;2:zqaa027. [DOI] [PubMed] [PMC]

90.

Bowersox SS, Luther R. Pharmacotherapeutic potential of ω-conotoxin MVIIA (SNX-111), an N-type neuronal calcium channel blocker found in the venom of Conus magus. Toxicon. 1998;36:1651–8. [DOI] [PubMed]

91.

Staats PS, Yearwood T, Charapata SG, Presley RW, Wallace MS, Byas-Smith M, et al. Intrathecal ziconotide in the treatment of refractory pain in patients with cancer or AIDS: a randomized controlled trial. JAMA. 2004;291:63–70. [DOI] [PubMed]

92.

Thompson SW, Bennett DL, Kerr BJ, Bradbury EJ, McMahon SB. Brain-derived neurotrophic factor is an endogenous modulator of nociceptive responses in the spinal cord. Proc Natl Acad Sci U S A. 1999;96:7714–8. [DOI] [PubMed] [PMC]

93.

Terlau H, Olivera BM. Conus venoms: a rich source of novel ion channel-targeted peptides. Physiol Rev. 2004;84:41–68. [DOI] [PubMed]

94.

Yeager RE, Yoshikami D, Rivier J, Cruz LJ, Miljanich GP. Transmitter release from presynaptic terminals of electric organ: inhibition by the calcium channel antagonist omega Conus toxin. J Neurosci. 1987;7:2390–6. [PubMed] [PMC]

95.

Doroshenko PA, Woppmann A, Miljanich G, Augustine GJ. Pharmacologically distinct presynaptic calcium channels in cerebellar excitatory and inhibitory synapses. Neuropharmacology. 1997;36:865–72. [DOI] [PubMed]

96.

Chu LF, Clark DJ, Angst MS. Opioid tolerance and hyperalgesia in chronic pain patients after one month of oral morphine therapy: a preliminary prospective study. J Pain. 2006;7:43–8. [DOI] [PubMed]

97.

Kristipati R, Nádasdi L, Tarczy-Hornoch K, Lau K, Miljanich GP, Ramachandran J, et al. Characterization of the binding of omega-conopeptides to different classes of non-L-type neuronal calcium channels. Mol Cell Neurosci. 1994;5:219–28. [DOI] [PubMed]

98.

Deer TR, Pope JE, Hanes MC, McDowell GC. Intrathecal therapy for chronic pain: a review of morphine and ziconotide as firstline options. Pain Med. 2019;20:784–98. [DOI] [PubMed] [PMC]

99.

Dray A. Neuropathic pain: emerging treatments. Br J Anaesth. 2008;101:48–58. [DOI] [PubMed]

100.

Malmberg AB, Yaksh TL. Effect of continuous intrathecal infusion of omega-conopeptides, N-type calcium-channel blockers, on behavior and antinociception in the formalin and hot-plate tests in rats. Pain. 1995;60:83–90. [DOI] [PubMed]

101.

Saegusa H, Matsuda Y, Tanabe T. Effects of ablation of N- and R-type Ca²⁺ channels on pain transmission. Neurosci Res. 2002;43:1–7. [DOI] [PubMed]

102.

Nestler EJ, Alreja M, Aghajanian GK. Molecular and cellular mechanisms of opiate action: studies in the rat locus coeruleus. Brain Res Bull. 1994;35:521–8. [DOI] [PubMed]

103.

Attali B, Saya D, Nah SY, Vogel Z. Kappa opiate agonists inhibit Ca²⁺ influx in rat spinal cord-dorsal root ganglion cocultures. Involvement of a GTP-binding protein. J Biol Chem. 1989;264:347–53. [DOI] [PubMed]

104.

Adams DJ, Callaghan B, Berecki G. Analgesic conotoxins: block and G protein-coupled receptor modulation of N-type (Ca_V2.2) calcium channels. Br J Pharmacol. 2012;166:486–500. [DOI] [PubMed] [PMC]

105.

Pirec V, Laurito CE, Lu Y, Yeomans DC. The combined effects of N-type calcium channel blockers and morphine on Aδ versus C fiber mediated nociception. Anesth Analg. 2001;92:239–43. [DOI] [PubMed]

106.

Zamponi GW, McCleskey EW. Splicing it up: a variant of the N-type calcium channel specific for pain. Neuron. 2004;41:3–4. [DOI] [PubMed]

107.

Dunlap K, Fischbach G. Neurotransmitters decrease the calcium component of sensory neurone action potentials. Nature. 1978;276:837–9. [DOI] [PubMed]

108.

Dunlap K, Fischbach GD. Neurotransmitters decrease the calcium conductance activated by depolarization of embryonic chick sensory neurones. J Physiol. 1981;317:519–35. [DOI] [PubMed] [PMC]

109.

Zamponi GW, Lewis RJ, Todorovic SM, Arneric SP, Snutch TP. Role of voltage-gated calcium channels in ascending pain pathways. Brain Res Rev. 2009;60:84–9. [DOI] [PubMed] [PMC]

110.

Zamponi GW, Currie KP. Regulation of Ca_V2 calcium channels by G protein coupled receptors. Biochim Biophys Acta. 2013;1828:1629–43. [DOI] [PubMed] [PMC]

111.

Currie KP. G protein modulation of Ca_V2 voltage-gated calcium channels. Channels. 2010;4:497–509. [DOI] [PubMed] [PMC]

112.

Altier C, Zamponi GW. Signaling complexes of voltage-gated calcium channels and G protein-coupled receptors. J Recept Signal Transduct Res. 2008;28:71–81. [DOI] [PubMed]

113.

Tedford HW, Zamponi GW. Direct G protein modulation of Ca_v2 calcium channels. Pharmacol Rev. 2006;58:837–62. [DOI] [PubMed]

114.

Enna SJ, McCarson KE. The role of GABA in the mediation and perception of pain. Adv Pharmacol. 2006;54:1–27. [DOI] [PubMed]

115.

Page AJ, O’Donnell TA, Blackshaw LA. Inhibition of mechanosensitivity in visceral primary afferents by GABA_B receptors involves calcium and potassium channels. Neuroscience. 2006;137:627–36. [DOI] [PubMed]

116.

Schwenk J, Metz M, Zolles G, Turecek R, Fritzius T, Bildl W, et al. Native GABA_B receptors are heteromultimers with a family of auxiliary subunits. Nature. 2010;465:231–5. [DOI] [PubMed]

117.

Bettler B, Kaupmann K, Mosbacher J, Gassmann M. Molecular structure and physiological functions of GABA_B receptors. Physiol Rev. 2004;84:835–67. [DOI] [PubMed]

118.

Page AJ, Blackshaw LA. GABA_B receptors inhibit mechanosensitivity of primary afferent endings. J Neurosci. 1999;19:8597–602. [DOI] [PubMed] [PMC]

119.

Patel S, Naeem S, Kesingland A, Froestl W, Capogna M, Urban L, et al. The effects of GABA_B agonists and gabapentin on mechanical hyperalgesia in models of neuropathic and inflammatory pain in the rat. Pain. 2001;90:217–26. [DOI] [PubMed]

120.

Smith GD, Harrison SM, Birch PJ, Elliott PJ, Malcangio M, Bowery NG. Increased sensitivity to the antinociceptive activity of (±)-baclofen in an animal model of chronic neuropathic, but not chronic inflammatory hyperalgesia. Neuropharmacology. 1994;33:1103–8. [DOI] [PubMed]

121.

Campbell V, Berrow N, Dolphin AC. GABA_B receptor modulation of Ca²⁺ currents in rat sensory neurones by the G protein G₀: antisense oligonucleotide studies. J Physiol. 1993;470:1–11. [DOI] [PubMed] [PMC]

122.

Menon-Johansson AS, Berrow N, Dolphin AC. G_o transduces GABA_B-receptor modulation of N-type calcium channels in cultured dorsal root ganglion neurons. Pflügers Arch. 1993;425:335–43. [DOI] [PubMed]

123.

Morishita R, Kato K, Asano T. GABA_B receptors couple to G proteins G_o, G^*_o and G•_i1 but not to G_i2. FEBS Lett. 1990;271:231–5. [DOI] [PubMed]

124.

Herlitze S, Garcia D, Mackie K, Hille B, Scheuer T, Catterall WA. Modulation of Ca²⁺ channels βγ G-protein py subunits. Nature. 1996:380;258–62. [DOI] [PubMed]

125.

Ikeda S. Voltage-dependent modulation of N-type calcium channels by G-protein βγ subunits. Nature. 1996;380:255–8. [DOI] [PubMed]

126.

Bean BP. Neurotransmitter inhibition of neuronal calcium currents by changes in channel voltage dependence. Nature. 1989;340:153–6. [DOI] [PubMed]

127.

Park J, Luo ZD. Calcium channel functions in pain processing. Channels. 2010;4:510–7. [DOI] [PubMed] [PMC]

128.

Price N, Namdari R, Neville J, Proctor KJ, Kaber S, Vest J, et al. Safety and efficacy of a topical sodium channel inhibitor (TV-45070) in patients with postherpetic neuralgia (PHN): a randomized, controlled, proof-of-concept, crossover study, with a subgroup analysis of the Nav1.7 R1150W genotype. Clin J Pain. 2017;33:310–8. [DOI] [PubMed] [PMC]

129.

McGivern JG. Targeting N-type and T-type calcium channels for the treatment of pain. Drug Discov Today. 2006;11:245–53. [DOI] [PubMed]

130.

Li ZM, Chen LX, Li H. Voltage-gated sodium channels and blockers: an overview and where will they go? Curr Med Sci. 2019;39:863–73. [DOI] [PubMed]

131.

Mould J, Yasuda T, Schroeder CI, Beedle AM, Doering CJ, Zamponi GW, et al. The α₂δ auxiliary subunit reduces affinity of ω-conotoxins for recombinant N-type (Ca_v2.2) calcium channels. J Biol Chem. 2004;279:34705–14. [DOI] [PubMed]

132.

Wright CE, Robertson AD, Whorlow SL, Angus JA. Cardiovascular and autonomic effects of ω-conotoxins MVIIA and CVID in conscious rabbits and isolated tissue assays. Br J Pharmacol. 2000;131:1325–36. [DOI] [PubMed] [PMC]

133.

Hwang SM, Jo YY, Cohen CF, Kim YH, Berta T, Park CK. Venom peptide toxins targeting the outer pore region of transient receptor potential vanilloid 1 in pain: implications for analgesic drug development. Int J Mol Sci. 2022;23:5772. [DOI] [PubMed] [PMC]

134.

Dib-Hajj SD, Rush AM, Cummins TR, Hisama FM, Novella S, Tyrrell L, et al. Gain-of-function mutation in Na_v1.7 in familial erythromelalgia induces bursting of sensory neurons. Brain. 2005;128:1847–54. [DOI] [PubMed]

135.

Novakovic SD, Tzoumaka E, McGivern JG, Haraguchi M, Sangameswaran L, Gogas KR, et al. Distribution of the tetrodotoxin-resistant sodium channel PN3 in rat sensory neurons in normal and neuropathic conditions. J Neurosci. 1998;18:2174–87. [DOI] [PubMed] [PMC]

136.

Dib-Hajj SD, Fjell J, Cummins TR, Zheng Z, Fried K, LaMotte R, et al. Plasticity of sodium channel expression in DRG neurons in the chronic constriction injury model of neuropathic pain. Pain. 1999;83:591–600. [DOI] [PubMed]

137.

Zhao P, Barr TP, Hou Q, Dib-Hajj SD, Black JA, Albrecht PJ, et al. Voltage-gated sodium channel expression in rat and human epidermal keratinocytes: evidence for a role in pain. Pain. 2008;139:90–105. [DOI] [PubMed]

138.

Bennett DL, Woods CG. Painful and painless channelopathies. Lancet Neurol. 2014;13:587–99. [DOI] [PubMed]

139.

Zhang N, Inan S, Cowan A, Sun R, Wang JM, Rogers TJ, et al. A proinflammatory chemokine, CCL3, sensitizes the heat- and capsaicin-gated ion channel TRPV1. Proc Natl Acad Sci U S A. 2005;102:4536–41. [DOI] [PubMed] [PMC]

140.

Obreja O, Rathee PK, Lips KS, Distler C, Kress M. IL-1 beta potentiates heat-activated currents in rat sensory neurons: involvement of IL-1RI, tyrosine kinase, and protein kinase C. FASEB J. 2002;16:1497–503. [DOI] [PubMed]

141.

Jang Y, Kim M, Hwang SW. Molecular mechanisms underlying the actions of arachidonic acid-derived prostaglandins on peripheral nociception. J Neuroinflammation. 2020;17:30. [DOI] [PubMed] [PMC]

142.

Słoniecka M, Le Roux S, Boman P, Byström B, Zhou Q, Danielson P. Expression profiles of neuropeptides, neurotransmitters, and their receptors in human keratocytes in vitro and in situ. PLoS One. 2015;10:e0134157. [DOI] [PubMed] [PMC]

143.

Denda M, Fujiwara S, Hibino T. Expression of voltage-gated calcium channel subunit α1C in epidermal keratinocytes and effects of agonist and antagonists of the channel on skin barrier homeostasis. Exp Dermatol. 2006;15:455–60. [DOI] [PubMed]

144.

Kumamoto J, Goto M, Denda S, Nakatani M, Takasugi Y, Tsuchiya K, et al. External negative electric potential accelerates exocytosis of lamellar bodies in human skin ex vivo. Exp Dermatol. 2013;22:421–3. [DOI] [PubMed]

145.

Jang JH, Nam TS, Jun J, Jung SJ, Kim DW, Leem JW. Peripheral NMDA receptors mediate antidromic nerve stimulation-induced tactile hypersensitivity in the rat. Mediators Inflamm. 2015;2015:793624. [DOI] [PubMed] [PMC]

146.

Warncke T, Jørum E, Stubhaug A. Local treatment with the N-methyl-D-aspartate receptor antagonist ketamine, inhibit development of secondary hyperalgesia in man by a peripheral action. Neurosci Lett. 1997;227:1–4. [DOI] [PubMed]

147.

Morhenn VB, Murakami M, O’Grady T, Nordberg J, Gallo RL. Characterization of the expression and function of N-methyl-D-aspartate receptor in keratinocytes. Exp Dermatol. 2004;13:505–11. [DOI] [PubMed]

148.

Ma W, Chabot JG, Vercauteren F, Quirion R. Injured nerve-derived COX2/PGE2 contributes to the maintenance of neuropathic pain in aged rats. Neurobiol Aging. 2010;31:1227–37. [DOI] [PubMed]

149.

Ahmed SU, Zhang Y, Chen L, Cohen A, St Hillary K, Vo T, et al. Effect of 1.5% topical diclofenac on clinical neuropathic pain. Anesthesiology. 2015;123:191–8. [DOI] [PubMed]

150.

Derry S, Wiffen PJ, Kalso EA, Bell RF, Aldington D, Phillips T, et al. Topical analgesics for acute and chronic pain in adults - an overview of Cochrane reviews. Cochrane Database Syst Rev. 2017;5:CD008609. [DOI] [PubMed] [PMC]

151.

Nigam R, El-Nour H, Amatya B, Nordlind K. GABA and GABAA receptor expression on immune cells in psoriasis: a pathophysiological role. Arch Dermatol Res. 2010;302:507–15. [DOI] [PubMed]

152.

Cevikbas F, Braz JM, Wang X, Solorzano C, Sulk M, Buhl T, et al. Synergistic antipruritic effects of gamma aminobutyric acid A and B agonists in a mouse model of atopic dermatitis. J Allergy Clin Immunol. 2017;140:454–64.e2. [DOI] [PubMed] [PMC]

153.

Ngo DH, Vo TS. An updated review on pharmaceutical properties of gamma-aminobutyric acid. Molecules. 2019;24:2678. [DOI] [PubMed] [PMC]

154.

Wu C, Qin X, Du H, Li N, Ren W, Peng Y. The immunological function of GABAergic system. Front Biosci (Landmark Ed). 2017;22:1162–72. [DOI] [PubMed]

155.

Irifune M, Sato T, Kamata Y, Nishikawa T, Dohi T, Kawahara M. Evidence for GABA_A receptor agonistic properties of ketamine: convulsive and anesthetic behavioral models in mice. Anesth Analg. 2000;91:230–6. [DOI] [PubMed]

156.

Granger P, Biton B, Faure C, Vige X, Depoortere H, Graham D, et al. Modulation of the gamma-aminobutyric acid type A receptor by the antiepileptic drugs carbamazepine and phenytoin. Mol Pharmacol. 1995;47:1189–96. [PubMed]

157.

Whitehead RA, Puil E, Ries CR, Schwarz SK, Wall RA, Cooke JE, et al. GABAB receptor-mediated selective peripheral analgesia by the non-proteinogenic amino acid, isovaline. Neuroscience. 2012;213:154–60. [DOI] [PubMed]

158.

Kopsky DJ, Keppel Hesselink JM. Neuropathic pain as a result of acromegaly, treated with topical baclofen cream. J Pain Symptom Manage. 2013;46:e4–5. [DOI] [PubMed]

159.

Barton DL, Wos EJ, Qin R, Mattar BI, Green NB, Lanier KS, et al. A double-blind, placebo-controlled trial of a topical treatment for chemotherapy-induced peripheral neuropathy: NCCTG trial N06CA. Support Care Cancer. 2011;19:833–41. [DOI] [PubMed] [PMC]

160.

Buerkle H. Peripheral anti-nociceptive action of α₂-adrenoceptor agonists. Best Pract Res Clin Anaesthesiol. 2000;14:411–8. [DOI]

161.

Riedl MS, Schnell SA, Overland AC, Chabot-Doré AJ, Taylor AM, Ribeiro-da-Silva A, et al. Coexpression of α_2A-adrenergic and δ-opioid receptors in substance P-containing terminals in rat dorsal horn. J Comp Neurol. 2009;513:385–98. [DOI] [PubMed] [PMC]

162.

Shi TJ, Winzer-Serhan U, Leslie F, Hökfelt T. Distribution and regulation of α₂-adrenoceptors in rat dorsal root ganglia. PAIN^®. 2000;84:319–30. [DOI] [PubMed]

163.

Kawasaki T, Kawasaki C, Ueki M, Hamada K, Habe K, Sata T. Dexmedetomidine suppresses proinflammatory mediator production in human whole blood in vitro. J Trauma Acute Care Surg. 2013;74:1370–5. [DOI] [PubMed]

164.

Eisenstein TK. The role of opioid receptors in immune system function. Front Immunol. 2019;10:2904. [DOI] [PubMed] [PMC]

165.

Smith MT, Wyse BD, Edwards SR, El-Tamimy M, Gaetano G, Gavin P. Topical application of a novel oxycodone gel formulation (tocopheryl phosphate mixture) in a rat model of peripheral inflammatory pain produces localized pain relief without significant systemic exposure. J Pharm Sci. 2015;104:2388–96. [DOI] [PubMed]

166.

Sehgal N, Smith HS, Manchikanti L. Peripherally acting opioids and clinical implications for pain control. Pain Physician. 2011;14:249–58. [DOI] [PubMed]

167.

Maldonado R, Baños JE, Cabañero D. The endocannabinoid system and neuropathic pain. Pain. 2016;157:S23–32. [DOI] [PubMed]

168.

Lötsch J, Weyer-Menkhoff I, Tegeder I. Current evidence of cannabinoid-based analgesia obtained in preclinical and human experimental settings. Eur J Pain. 2018;22:471–84. [DOI] [PubMed]

169.

Bruni N, Della Pepa C, Oliaro-Bosso S, Pessione E, Gastaldi D, Dosio F. Cannabinoid delivery systems for pain and inflammation treatment. Molecules. 2018;23:2478. [DOI] [PubMed] [PMC]

170.

Forouzanfar F, Hosseinzadeh H. Medicinal herbs in the treatment of neuropathic pain: a review. Iran J Basic Med Sci. 2018;21:347–58. [DOI] [PubMed] [PMC]

171.

Muthuraman A, Singh N, Jaggi AS. Effect of hydroalcoholic extract of Acorus calamus on tibial and sural nerve transection-induced painful neuropathy in rats. J Nat Med. 2011;65:282–92. [DOI] [PubMed]

172.

Muthuraman A, Singh N. Attenuating effect of Acorus calamus extract in chronic constriction injury induced neuropathic pain in rats: an evidence of anti-oxidative, anti-inflammatory, neuroprotective and calcium inhibitory effects. BMC Complement Altern Med. 2011;11:24. [DOI] [PubMed] [PMC]

173.

Mohammad Reza S, Hamideh M, Zahra S. The nociceptive and anti-inflammatory effects of Artemisia dracunculus L. aqueous extract on fructose fed male rats. Evid Based Complement Alternat Med. 2015;2015:895417. [DOI] [PubMed] [PMC]

174.

Watcho P, Stavniichuk R, Ribnicky DM, Raskin I, Obrosova IG. High-fat diet-induced neuropathy of prediabetes and obesity: effect of PMI-5011, an ethanolic extract of Artemisia dracunculus L. Mediators Inflamm. 2010;2010:268547. [DOI] [PubMed] [PMC]

175.

Thiagarajan VR, Shanmugam P, Krishnan UM, Muthuraman A, Singh N. Antinociceptive effect of Butea monosperma on vincristine-induced neuropathic pain model in rats. Toxicol Ind Health. 2013;29:3–13. [DOI] [PubMed]

176.

Thiagarajan VR, Shanmugam P, Krishnan UM, Muthuraman A, Singh N. Ameliorative potential of Butea monosperma on chronic constriction injury of sciatic nerve induced neuropathic pain in rats. An Acad Bras Cienc. 2012;84:1091–104. [DOI] [PubMed]

177.

Marzouk B, Marzouk Z, Haloui E, Fenina N, Bouraoui A, Aouni M. Screening of analgesic and anti-inflammatory activities of Citrullus colocynthis from southern Tunisia. J Ethnopharmacol. 2010;128:15–9. [DOI] [PubMed]

178.

Heydari M, Homayouni K, Hashempur MH, Shams M. Topical Citrullus colocynthis (bitter apple) extract oil in painful diabetic neuropathy: a double-blind randomized placebo-controlled clinical trial. J Diabetes. 2016;8:246–52. [DOI] [PubMed]

179.

Zhao X, Xu Y, Zhao Q, Chen CR, Liu AM, Huang ZL. Curcumin exerts antinociceptive effects in a mouse model of neuropathic pain: descending monoamine system and opioid receptors are differentially involved. Neuropharmacology. 2012;62:843–54. [DOI] [PubMed]

180.

Moini Zanjani T, Ameli H, Labibi F, Sedaghat K, Sabetkasaei M. The attenuation of pain behavior and serum COX-2 concentration by curcumin in a rat model of neuropathic pain. Korean J Pain. 2014;27:246–52. [DOI] [PubMed] [PMC]

181.

Amin B, Hosseinzadeh H. Evaluation of aqueous and ethanolic extracts of saffron, Crocus sativus L., and its constituents, safranal and crocin in allodynia and hyperalgesia induced by chronic constriction injury model of neuropathic pain in rats. Fitoterapia. 2012;83:888–95. [DOI] [PubMed]

182.

Amin B, Abnous K, Motamedshariaty V, Hosseinzadeh H. Attenuation of oxidative stress, inflammation and apoptosis by ethanolic and aqueous extracts of Crocus sativus L. stigma after chronic constriction injury of rats. An Acad Bras Cienc. 2014;86:1821–32. [DOI] [PubMed]

183.

Karimi G, Hosseinzadeh H, Rassoulzadeh M, Razavi BM, Taghiabadi E. Antinociceptive effect of Elaeagnus angustifolia fruits on sciatic nerve ligated mice. Iran J Basic Med Sci. 2010;13:97–101.

184.

Ramezani M, Hosseinzadeh H, Daneshmand N. Antinociceptive effect of Elaeagnus angustifolia fruit seeds in mice. Fitoterapia. 2001;72:255–62. [DOI] [PubMed]

185.

Kim YS, Park HJ, Kim TK, Moon DE, Lee HJ. The effects of Ginkgo biloba extract EGb 761 on mechanical and cold allodynia in a rat model of neuropathic pain. Anesth Analg. 2009;108:1958–63. [DOI] [PubMed]

186.

Taliyan R, Sharma PL. Protective effect and potential mechanism of Ginkgo biloba extract EGb 761 on STZ-induced neuropathic pain in rats. Phytother Res. 2012;26:1823–9. [DOI] [PubMed]

187.

Matsumoto K, Narita M, Muramatsu N, Nakayama T, Misawa K, Kitajima M, et al. Orally active opioid μ/δ dual agonist MGM-16, a derivative of the indole alkaloid mitragynine, exhibits potent antiallodynic effect on neuropathic pain in mice. J Pharmacol Exp Ther. 2014;348:383–92. [DOI] [PubMed] [PMC]

188.

Carpenter JM, Criddle CA, Craig HK, Ali Z, Zhang Z, Khan IA, et al. Comparative effects of Mitragyna speciosa extract, mitragynine, and opioid agonists on thermal nociception in rats. Fitoterapia. 2016;109:87–90. [DOI] [PubMed]

189.

Jain V, Pareek A, Paliwal N, Ratan Y, Jaggi AS, Singh N. Antinociceptive and antiallodynic effects of Momordica charantia L. in tibial and sural nerve transection-induced neuropathic pain in rats. Nutr Neurosci. 2014;17:88–96. [DOI] [PubMed]

190.

Amin B, Taheri MM, Hosseinzadeh H. Effects of intraperitoneal thymoquinone on chronic neuropathic pain in rats. Planta Med. 2014;80:1269–77. [DOI] [PubMed]

191.

Tewari S, Salman M, Thadani S, Singh S, Ahmad A. A study of pregabalin, tramadol, their combination and Nigella sativa in neuropathic pain in rats. Int J Pharm Sci Res. 2015;6:4406. [DOI]

192.

Xu H, Arita H, Hayashida M, Zhang L, Sekiyama H, Hanaoka K. Pain-relieving effects of processed Aconiti tuber in CCI-neuropathic rats. J Ethnopharmacol. 2006;103:392–7. [DOI] [PubMed]

193.

Dallazen JL, Maria-Ferreira D, da Luz BB, Nascimento AM, Cipriani TR, de Souza LM, et al. Distinct mechanisms underlying local antinociceptive and pronociceptive effects of natural alkylamides from Acmella oleracea compared to synthetic isobutylalkyl amide. Fitoterapia. 2018;131:225–35. [DOI] [PubMed]

194.

Garg G, Adams JD. Treatment of neuropathic pain with plant medicines. Chin J Integr Med. 2012;18:565–70. [DOI] [PubMed]

195.

Singh H, Arora R, Arora S, Singh B. Ameliorative potential of Alstonia scholaris (Linn.) R. Br. against chronic constriction injury-induced neuropathic pain in rats. BMC Complement Altern Med. 2017;17:63. [DOI] [PubMed] [PMC]

196.

Que W, Wu Z, Chen M, Zhang B, You C, Lin H, et al. Molecular mechanism of Gelsemium elegans (Gardner and Champ.) Benth. against neuropathic pain based on network pharmacology and experimental evidence. Front Pharmacol. 2022;12:792932. [DOI] [PubMed] [PMC]

197.

Samandar F, Tehranizadeh ZA, Saberi MR, Chamani J. CB1 as a novel target for Ginkgo biloba’s terpene trilactone for controlling chemotherapy-induced peripheral neuropathy (CIPN). J Mol Model. 2022;28:283. [DOI] [PubMed]

198.

Chen Y, Feng Z, Shen M, Lin W, Wang Y, Wang S, et al. Insight into Ginkgo biloba L. extract on the improved spatial learning and memory by chemogenomics knowledgebase, molecular docking, molecular dynamics simulation, and bioassay validations. ACS Omega. 2020;5:2428–39. [DOI] [PubMed] [PMC]

199.

Lim DW, Kim JG, Kim YT. Analgesic effect of Indian gooseberry (Emblica officinalis fruit) extracts on postoperative and neuropathic pain in rats. Nutrients. 2016;8:760. [DOI] [PubMed] [PMC]

200.

Palit P, Mukherjee D, Mahanta P, Shadab M, Ali N, Roychoudhury S, et al. Attenuation of nociceptive pain and inflammatory disorders by total steroid and terpenoid fraction of Euphorbia tirucalli Linn root in experimental in vitro and in vivo model. Inflammopharmacology. 2018;26:235–50. [DOI] [PubMed]

201.

Xu Y, Qiu HQ, Liu H, Liu M, Huang ZY, Yang J, et al. Effects of koumine, an alkaloid of Gelsemium elegans Benth., on inflammatory and neuropathic pain models and possible mechanism with allopregnanolone. Pharmacol Biochem Behav. 2012;101:504–14. [DOI] [PubMed]

202.

Liu M, Shen J, Liu H, Xu Y, Su YP, Yang J, et al. Gelsenicine from Gelsemium elegans attenuates neuropathic and inflammatory pain in mice. Biol Pharm Bull. 2011;34:1877–80. [DOI] [PubMed]

203.

Chen H, Ma D, Zhang H, Tang Y, Wang J, Li R, et al. Antinociceptive effects of oleuropein in experimental models of neuropathic pain in male rats. Korean J Pain. 2021;34:35–46. [DOI] [PubMed] [PMC]

204.

Zhu C, Li W, Xu F, Li M, Yang L, Hu XY, et al. Effects of Ginkgo Biloba extract EGb-761 on neuropathic pain in mice: involvement of opioid system. Phytother Res. 2016;30:1809–16. [DOI] [PubMed]

205.

Jain V, Pareek A, Ratan Y, Singh N. Standardized fruit extract of Momordica charantia L protect against vincristine induced neuropathic pain in rats by modulating GABAergic action, antimitotoxic, NOS inhibition, anti-inflammatory and antioxidative activity. S Afr J Bot. 2015;97:123–32. [DOI]

206.

Taïwe GS, Bum EN, Talla E, Dimo T, Dawe A, Sinniger V, et al. Nauclea latifolia Smith (Rubiaceae) exerts antinociceptive effects in neuropathic pain induced by chronic constriction injury of the sciatic nerve. J Ethnopharmacol. 2014;151:445–51. [DOI] [PubMed]

207.

Taïwe GS, Bum EN, Talla E, Dimo T, Weiss N, Sidiki N, et al. Antipyretic and antinociceptive effects of Nauclea latifolia root decoction and possible mechanisms of action. Pharm Biol. 2011;49:15–25. [DOI] [PubMed] [PMC]

208.

Kaur G, Jaggi AS, Singh N. Exploring the potential effect of Ocimum sanctum in vincristine-induced neuropathic pain in rats. J Brachial Plex Peripher Nerve Inj. 2010;5:e3–11. [DOI] [PubMed] [PMC]

209.

Kaeidi A, Esmaeili-Mahani S, Sheibani V, Abbasnejad M, Rasoulian B, Hajializadeh Z, et al. Olive (Olea europaea L.) leaf extract attenuates early diabetic neuropathic pain through prevention of high glucose-induced apoptosis: in vitro and in vivo studies. J Ethnopharmacol. 2011;136:188–96. [DOI] [PubMed]

210.

Wang L, Jiang Y, Han T, Zheng C, Qin L. A phytochemical, pharmacological and clinical profile of Paederia foetida and P. scandens. Nat Prod Commun. 2014;9:879–86. [DOI] [PubMed]

211.

Guerrero-Solano JA, Jaramillo-Morales OA, Velázquez-González C, De la O-Arciniega M, Castañeda-Ovando A, Betanzos-Cabrera G, et al. Pomegranate as a potential alternative of pain management: a review. Plants. 2020;9:419. [DOI] [PubMed] [PMC]

212.

Jothy SL, Torey A, Darah I, Choong YS, Saravanan D, Chen Y, et al. Cassia spectabilis (DC) Irwin et Barn: a promising traditional herb in health improvement. Molecules. 2012;17:10292–305. [DOI] [PubMed] [PMC]

213.

Hajializadeh Z, Nasri S, Kaeidi A, Sheibani V, Rasoulian B, Esmaeili-Mahani S. Inhibitory effect of Thymus caramanicus Jalas on hyperglycemia-induced apoptosis in in vitro and in vivo models of diabetic neuropathic pain. J Ethnopharmacol. 2014;153:596–603. [DOI] [PubMed]

214.

Gautam M, Ramanathan M. Saponins of Tribulus terrestris attenuated neuropathic pain induced with vincristine through central and peripheral mechanism. Inflammopharmacology. 2019;27:761–72. [DOI] [PubMed]

215.

Moghadam FH, Vakili-Zarch B, Shafiee M, Mirjalili A. Fenugreek seed extract treats peripheral neuropathy in pyridoxine induced neuropathic mice. EXCLI J. 2013;12:282–90. [PubMed] [PMC]

216.

Thiagarajan VR, Shanmugam P, Krishnan UM, Muthuraman A. Ameliorative potential of Vernonia cinerea on chronic constriction injury of sciatic nerve induced neuropathic pain in rats. An Acad Bras Cienc. 2014;86:1435–50. [DOI] [PubMed]

217.

Vink S, Alewood PF. Targeting voltage-gated calcium channels: developments in peptide and small-molecule inhibitors for the treatment of neuropathic pain. Br J Pharmacol. 2012;167:970–89. [DOI] [PubMed] [PMC]

218.

Raj S, Manchanda R, Bhandari M, Alam MS. Review on natural bioactive products as radioprotective therapeutics: present and past perspective. Curr Pharm Biotechnol. 2022;23:1721–38. [DOI] [PubMed]

219.

Atanassoff PG, Hartmannsgruber MW, Thrasher J, Wermeling D, Longton W, Gaeta R, et al. Ziconotide, a new N-type calcium channel blocker, administered intrathecally for acute postoperative pain. Reg Anesth Pain Med. 2000;25:274–8. [DOI] [PubMed]

220.

Waziri A, Bharti C, Aslam M, Jamil P, Mirza MA, Javed MN, et al. Probiotics for the chemoprotective role against the toxic effect of cancer chemotherapy. Anticancer Agents Med Chem. 2022;22:654–67. [DOI] [PubMed]

221.

Knutsen LJ, Hobbs CJ, Earnshaw CG, Fiumana A, Gilbert J, Mellor SL, et al. Synthesis and SAR of novel 2-arylthiazolidinones as selective analgesic N-type calcium channel blockers. Bioorg Med Chem Lett. 2007;17:662–7. [DOI] [PubMed]

222.

Mishra S, Sharma S, Javed MN, Pottoo FH, Barkat MA, Harshita, et al. Bioinspired nanocomposites: applications in disease diagnosis and treatment. Pharm Nanotechnol. 2019;7:206–19. [DOI] [PubMed]

223.

Javed MN, Dahiya ES, Ibrahim AM, Alam MS, Khan FA, Pottoo FH. Recent advancement in clinical application of nanotechnological approached targeted delivery of herbal drugs. In: Beg S, Barkat M, Ahmad F, editor. Nanophytomedicine. Singapore: Springer; 2020. pp. 151–72. [DOI]

224.

Javed MN, Alam MS, Pottoo FH, inventors; Javed MN, Alam MS, Pottoo FH, assignees. Metallic nanoparticle alone and/or in combination as novel agent for the treatment of uncontrolled electric conductance related disorders and/or seizure, epilepsy & convulsions. India patent WO2017060916. 2017 Apr 13..

225.

Javed MN, Pottoo FH, Shamim A, Hasnain MS, Alam MS. Design of experiments for the development of nanoparticles, nanomaterials, and nanocomposites. In: Beg S, editor. Design of experiments for pharmaceutical product development. Singapore: Springer; 2021. pp. 151–69. [DOI]

226.

Aslam M, Javed MN, Deeb HH, Nicola MK, Mirza MA, Alam MS, et al. Lipid nanocarriers for neurotherapeutics: introduction, challenges, blood-brain barrier, and promises of delivery approaches. CNS Neurol Disord Drug Targets. 2022;21:952–65. [DOI] [PubMed]

227.

Singhal S, Gupta M, Alam MS, Javed MN, Ansari JR. Carbon allotropes-based nanodevices: graphene in biomedical applications. In: Birla S, Singh N, Shukla NK, editor. Nanotechnology. Boca Raton: CRC Press; 2022. pp. 241–69. [DOI]

228.

Javed MN, Akhter MH, Taleuzzaman M, Faiyazudin M, Alam MS. Chapter 10—Cationic nanoparticles for treatment of neurological diseases. In: Barhoum A, Jeevanandam J, Danquah MK, editor. Fundamentals of bionanomaterials. Amsterdam: Elsevier; 2022. pp. 273–92. [DOI]

229.

Pandit J, Alam MS, Ansari JR, Singhal M, Gupta N, Waziri A, et al. Multifaced applications of nanoparticles in biological science. In: Pal K, Zaheer T, editor. Nanomaterials in the battle against pathogens and disease vectors. Boca Raton: CRC Press; 2022. pp. 17–50. [DOI]

230.

Naseh MF, Ansari JR, Alam MS, Javed MN. Sustainable nanotorus for biosensing and therapeutical applications. In: Shanker U, Hussain CM, Rani M, editor. Handbook of green and sustainable nanotechnology. Cham: Springer; 2022. pp. 1–21. [DOI]

231.

Ibrahim AM, Chauhan L, Bhardwaj A, Sharma A, Fayaz F, Kumar B, et al. Brain-derived neurotropic factor in neurodegenerative disorders. Biomedicines. 2022;10:1143. [DOI] [PubMed] [PMC]

232.

Kumari N, Daram N, Alam MS, Verma AK. Rationalizing the use of polyphenol nano-formulations in the therapy of neurodegenerative diseases. CNS Neurol Disord Drug Targets. 2022;21:966–76. [DOI] [PubMed]

233.

Bharti C, Alam MS, Javed MN, Saifullah MK, Almalki FA, Manchanda R. Silica based nanomaterial for drug delivery. In: Nimesh S, Gupta N, Chandra R, editor. Nanomaterials: evolution and advancement towards therapeutic drug delivery (Part II). Sharjah: Bentham Science Books; 2021. pp. 57–89. [DOI]