Attenuation of hyperalgesia in a rat model of neuropathic pain after intrathecal pre- or post-treatment with a neurokinin-1 antagonist.
Although many studies have demonstrated a role for substance P in pain, there have been conflicting reports implicating the involvement of substance P in neuropathic pain models. In this study, the non-peptide neurokinin-1 (NK-1) receptor antagonist, L-732,138 was chronically administered by intrathecal (i.t.) injection to rats with mono-neuropathy produced by sciatic nerve constriction. Rats exhibited tactile allodynia and cold hyperalgesia over a 16-day testing period. L-732,138 (5-200 nmol) administered i.t. prior to and for 3 consecutive days post-surgery attenuated the mechanical allodynia and cold hyperalgesia on days 4 and 8 post-surgery. The effects of i.t. L-732,138 were also determined in rats with established nerve injury-induced neuropathy. The NK-1 receptor antagonist was injected for 4 consecutive days starting on day 8 post-sciatic nerve injury. Administration of L-732,138 (5-200 nmol) i.t. produced both anti-allodynic and anti-hyperalgesic effects on day 12, but the effect was not permanent, as nociceptive thresholds were similar to controls by day 16. These results demonstrate that substance P is involved both in the induction and the maintenance of neuropathic pain and provides justification for the development and administration of substance P antagonists for the management of clinical neuropathic pain.
Cahill
Catherine M
CM
Pain Mechanisms Laboratory, Clinical Research Institute of Montreal, Montreal, Quebec, Canada Anesthesia Research Unit, Department of Anesthesia, McGill University, McIntyre Medical Sciences Building, Room 1203, 3655 Dummond Street, Montreal, Quebec, Canada H3G 1Y6 Department of Psychology, McGill University, Montreal, Quebec, Canada.
Coderre
Terence J
TJ
D000818:Animals; D003080:Cold Temperature; D004195:Disease Models, Animal; D006930:Hyperalgesia / Q000188:drug therapy*; D007278:Injections, Spinal; D008297:Male; D064729:Neurokinin-1 Receptor Antagonists; D009619:Nociceptors / Q000187:drug effects; D010812:Physical Stimulation; D051381:Rats; D020318:Rats, Long-Evans; D012585:Sciatica / Q000188:drug therapy*; D013373:Substance P / Q000502:physiology; D014364:Tryptophan / Q000031:analogs & derivatives / Q000494:pharmacology
D064729:Neurokinin-1 Receptor Antagonists; C086089:3,5-bis(trifluoromethyl)benzyl N-acetyltryptophan; D013373:Substance P; D014364:Tryptophan