Memory of pain: the effect of perineural resiniferatoxin.
The long-lasting imprint of acute pain in the central nervous system may contribute to the transition of acute pain to chronicity. The long-term potentiation (which is proposed as a mechanism of memory) and central sensitization were each reported as a form of synaptic plasticity, and both can be initiated by stimulation of C fibers. In the current study, we assessed nociceptive memory regarding hyperalgesia by measuring distant hyperalgesia after repeated carrageenan-induced inflammation. This approach was used to determine whether selective blockade of C fibers can prevent the development of a long-lasting imprint of hyperalgesia. In rat experiments, resiniferatoxin was administered percutaneously at the sciatic and saphenous nerves, and two crossover intraplantar injections of carrageenan into the hindpaws were performed 2 wk apart. Responses to noxious pressure and heat and changes in paw volumes were measured at various intervals during two carrageenan-induced inflammations. The experiments demonstrated that after recovery of hyperalgesia induced by the initial inflammation, repeated inflammation led to the development of a distant hyperalgesia that was absent during the initial inflammation. The maximum of distant hyperalgesia (decrease of noxious pressure threshold in the contralateral hindpaw from 141 +/- 23 g to 96 +/- 19 g; P < 0.0001) was reached 24 h after the second injection of carrageenan. The development of distant hyperalgesia during the repeated inflammation was completely prevented (P < 0.0002) by perineural resiniferatoxin (0.001%) administered before the initial injection of carrageenan. These results indicate that selective blockade of nociceptive fibers prevents formation of long-term hyperalgesia-related imprint in the central nervous system. Thus, pain memory can be preempted by selective and prolonged blockade of C-fibers.
Kissin
Igor
I
Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. kissin@zeus.bwh.harvard.edu
Freitas
Cristina F
CF
Bradley
Edwin L
EL
D000818:Animals; D002351:Carrageenan / Q000494:pharmacology; D002490:Central Nervous System / Q000473:pathology; D004224:Diterpenes / Q000494:pharmacology*; D006801:Humans; D006930:Hyperalgesia; D007249:Inflammation; D008297:Male; D008568:Memory; D009407:Nerve Block / Q000379:methods*; D010146:Pain / Q000188:drug therapy*; D010525:Peripheral Nerves / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012501:Saphenous Vein / Q000473:pathology*; D012584:Sciatic Nerve / Q000473:pathology*
D004224:Diterpenes; D002351:Carrageenan; C024353:resiniferatoxin