Since the first description made by Descartes in his “Les Passions de l'âme” (Passions of the soul) (Paris, 1649), the knowledge on pain has evolved enormously in its pathophysiologic and therapeutic aspects. The simple description made by Descartes was definitely well appealing and convincing. In fact, it was largely accepted till the middle of the 1990s, when Melzack and Wall described a different model, with more solid scientific and pathophysiological knowledge, even if just based on a theoretical model: the “Gate Control Theory” [1].

The theory, formulated to provide a mechanism for coding the nociceptive component of cutaneous sensory input, has changed the scientific approach to pain pathophysiology and pain therapy. The “gate control theory” has been largely criticized, deconstructed and reconstructed [2]. In any case, the clarity of the model and its description were such that the publication had immediate visibility and diffusion. For the very first time, the “theory” incorporated newly acquired concepts of presynaptic control of transmission from large and small sensory afferents. Moreover, it suggested the ability of descending control pathways to affect the perception of pain sensation.

Since then, several physiology and pathophysiology researches have been addressed to finally have scientific knowledge of the complex mechanism called “pain”. More recently, an interesting publication has summarized the physiological knowledge in a poetic and philosophical perspective [3]. While a further important publication has described with attention all the physiological knowledge related to pain perception, from the pathophysiological point of view [4]. Both articles have made clear that the Descartes theory was just a marginal part of the entire system. Finally, it is possible to say that the entire system is still not completely clear. In fact, the Nobel Prize of 2021 was awarded to two researchers, David Julius and Ardem Patapoutian, for their discoveries on receptors for touch and temperature that are crucial in the perception of what is described as “pain”.

One of the most intriguing aspects of this complex system is represented by the so called “neuropathic pain”. The concept of pain generated inside of the nervous system is old of several decades, and has been object of over 50.000 publications present on PubMed. That notwithstanding, it has still several aspects that are attracting the attention of the researchers, especially Neurologists, and Pain Physicians. At the moment, it seems very important to better understand the necessity of an interdisciplinary approach and its potentialities for a better management of the patients affected by neuropathic pain [5]. The influence of neuropathic pain in neurological disorders is also an attractive aspect [6]. The researchers are well aware of the several diagnostic difficulties affecting this part of Pain Medicine, and some recent publication is reporting interesting experiences [7]. Of course, the main interests are on the management, especially for some specific syndromes [8,9]. Still, there are scientific interests in new areas to better understand the intimate mechanisms of neuropathic pain, and the deep study of the sigma receptors may represent a new, important pathway to clarify several still unknown aspects, and their potentialities for a better therapeutic approach [10].

The main aim of this special issue is to stimulate the research on this important and still debated topic. Neuropathic pain cannot remain a terrible enemy of the patients, causing sufferance and affecting people that frequently have other concomitant pathologies. The multidisciplinary approach, which may derive from the proposal of this special issue, might definitely grant some benefits to them.

References

1. Melzack R, Wall PD. Pain mechanisms: a new theory. Science. 1965 Nov 19;150(3699):971-9. doi: 10.1126/science.150.3699.971.

2. Mendell LM. Constructing and deconstructing the gate theory of pain. Pain. 2014 Feb;155(2):210-216. doi: 10.1016/j.pain.2013.12.010.

3. Woolf CJ. What is this thing called pain? J Clin Invest. 2010;120(11):3742-4. doi: 10.1172/JCI45178.

4. Kuner R, Kuner T. Cellular Circuits in the Brain and Their Modulation in Acute and Chronic Pain. Physiol Rev. 2021 Jan 1;101(1):213-258. doi: 10.1152/physrev.00040.2019.

5. Szewczyk AK, Jamroz-Wiśniewska A, Haratym N, Rejdak K. Neuropathic pain and chronic pain as an underestimated interdisciplinary problem. Int J Occup Med Environ Health. 2022 Jun 8;35(3):249-264. doi: 10.13075/ijomeh.1896.01676.

6. Mitsikostas DD, Moka E, Orrillo E, Aurilio C, Vadalouca A, Paladini A, Varrassi G. Neuropathic Pain in Neurologic Disorders: A Narrative Review. Cureus. 2022 Feb 20;14(2):e22419. doi: 10.7759/cureus.22419.

7. Kritikou P, Vadalouca A, Rekatsina M, Varrassi G, Siafaka I. The Diagnostic Odyssey of Patients with Chronic Neuropathic Pain-Expert Opinion of Greek Pain Specialists. Clin Pract. 2023 Jan 27;13(1):166-176. doi: 10.3390/clinpract13010015.

8. Pergolizzi JV Jr, Gharibo C, Magnusson P, Breve F, LeQuang JA, Varrassi G. Pharmacotherapeutic management of trigeminal neuropathic pain: an update. Expert Opin Pharmacother. 2022;23(10):1155-1164. doi: 10.1080/14656566.2022.2087507.

9. Kouri M, Rekatsina M, Vadalouca A, Siafaka I, Vardas E, Papadopoulou E, Paladini A, Varrassi G. Pharmacological Management of Neuropathic Pain after Radiotherapy in Head and Neck Cancer Patients: A Systematic Review. J Clin Med. 2022 Aug 19;11(16):4877. doi: 10.3390/jcm11164877.

10. Pergolizzi J, Varrassi G, Coleman M, et al. The sigma enigma: A narrative review of sigma receptors. Cureus. 2023. DOI: 10.7759/cureus.35756

Keywords: Neuropathic pain, treatment, sigma receptors