Animal studies documented a correlation between increased TSP4 expression and behavioral hypersensitivity development in the spinal cord/DRG

StudyAnimals (species/types)ProceduresResults
Kim et al. [41], 2012Male young adult Harlan Sprague-Dawley ratsL5/6 SNLTSP4 expression increased in L5/6 DSC on the 2nd and 10th postoperative days. Tactile allodynia and thermal and mechanical hyperalgesia peaked on the 30th, 20th, and 10th postoperative days, respectively
TSP4 protein, 45 μg/rat, intrathecalTactile allodynia and thermal and mechanical hyperalgesia reached peak levels around the 3rd–4th post-injection days
Adult male THBS4 knockout miceL5 SNLTactile allodynia did not develop after SNL
Zeng et al. [98], 2013Adult female Sprague-Dawley ratsSCITSP4 expression in the L4–6 DSC significantly increased 30–40 days after SCI. Mechanical and thermal hyperalgesia reached peak levels approximately four weeks post-SCI
Li et al. [97], 2014Adult male Sprague-Dawley ratsCCI of the infraorbital nerveTSP4 expression in the C1/2 spinal cord and orofacial tactile allodynia peaked on the 3rd postoperative week
Crosby et al. [30], 2015Adult male Holtzman ratsC6/7 FJDTSP4 expression increased in the spinal cord on the 7th postoperative day. Tactile allodynia developed one day after surgery and persisted for seven days. Excitatory synapse density increased in the superficial DH
TSP4 protein, at different doses, intrathecalTactile allodynia developed at 30 μg/rat and higher doses of TSP4 protein and peaked three days after TSP4, 60 μg/rat, intrathecal
TSP4 protein, 60 μg/rat, intrathecal (3 days before FJD)A single dose (60 μg/rat) of TSP4 protein, administered three days before FJD, exacerbated the FJD-induced tactile allodynia
Pan et al. [73], 2015Male Sprague-Dawley ratsL5/6 SNL or SNITactile allodynia developed following SNL and SNI. TSP4 expression increased in neurons, the extracellular space, and DRG on the 2nd and 24th days after SNL and SNI surgery
Park et al. [93], 2016Adult male Harlan Sprague-Dawley ratsTSP4 protein, 45 μg/rat, intrathecalTactile allodynia that peaked on the 3rd day developed. mEPSCs increased in the L5 superficial spinal DH neurons
THBS4 knockout miceL4 SNLBehavioral hypersensitivity did not detect
Park et al. [99], 2018Male adult Harlan Sprague-Dawley ratsThe EGF-like domain of TSP4 protein, 10 μg/rat, intrathecalTactile allodynia and thermal hyperalgesia developed within two days and lasted for about one week (similar to that induced by full-length TSP4 proteins)
Yu et al. [100], 2018129sv adult male and female miceTSP4 protein, 5 μg/mouse, intrathecalTactile allodynia peaked on day 4 post-TSP4 injection, and excitatory synapses in DSC increased by approximately 37%
Düzenli et al. [95], 2022Wistar ratsCCI of the sciatic nerveOn the 4th postoperative day, TSP4 expression increased in the L4–6 spinal cord and tactile allodynia and mechanical and thermal hyperalgesia developed.

CCI: chronic construction injury; SCI: spinal cord injury; SNI: spared nerve injury