Spinal translocator protein (TSPO) modulates pain behavior in rats with CFA-induced monoarthritis.
Translocator protein 18 kDa (TSPO), previously known as the peripheral benzodiazepine receptor (PBR), is predominantly located in the mitochondrial outer membrane and plays an important role in steroidogenesis, immunomodulation, cell survival and proliferation. Previous studies have shown an increased expression of TSPO centrally in neuropathology, as well as in injured nerves. TSPO has also been implicated in modulation of nociception. In the present study, we examined the hypothesis that TSPO is involved in the initiation and maintenance of inflammatory pain using a rat model of Complete Freund's Adjuvant (CFA)-induced monoarthritis of the tibio-tarsal joint. Immunohistochemistry was performed using Iba-1 (microglia), NeuN (neurons), anti-Glial Fibrillary Acidic Protein, GFAP (astrocytes) and anti-PBR (TSPO) on Days 1, 7 and 14 after CFA-induced arthritis. Rats with CFA-induced monoarthritis showed mechanical allodynia and thermal hyperalgesia on the ipsilateral hindpaw, which correlated with the increased TSPO expression in ipsilateral laminae I-II on all experimental days. Iba-1 expression in the ipsilateral dorsal horn was also increased on Days 7 and 14. Moreover, TSPO was colocalized with Iba-1, GFAP and NeuN within the spinal cord dorsal horn. The TSPO agonist Ro5-4864, given intrathecally, dose-dependently retarded or prevented the development of mechanical allodynia and thermal hyperalgesia in rats with CFA-induced monoarthritis. These findings provide evidence that spinal TSPO is involved in the development and maintenance of inflammatory pain behaviors in rats. Thus, spinal TSPO may present a central target as a complementary therapy to reduce inflammatory pain.
Hernstadt
Hayley
H
Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Victoria 3010, Australia.
Wang
Shuxing
S
Lim
Grewo
G
Mao
Jianren
J
D000818:Animals; D001169:Arthritis, Experimental / Q000378:metabolism* / Q000503:physiopathology; D001522:Behavior, Animal / Q000502:physiology; D001570:Benzodiazepinones / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism*; D003292:Convulsants / Q000494:pharmacology; D005620:Freund's Adjuvant / Q000633:toxicity; D007839:Functional Laterality / Q000502:physiology; D006930:Hyperalgesia / Q000209:etiology / Q000378:metabolism; D007150:Immunohistochemistry; D007249:Inflammation / Q000139:chemically induced / Q000209:etiology / Q000378:metabolism; D008297:Male; D010146:Pain / Q000378:metabolism* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism*
D001570:Benzodiazepinones; D002352:Carrier Proteins; D003292:Convulsants; D011963:Receptors, GABA-A; C069997:Tspo protein, rat; C028513:4'-chlorodiazepam; D005620:Freund's Adjuvant