Epidural opioid analgesia in infant rats - II: responses to carrageenan and capsaicin

The aim of this study was to investigate the analgesic effects of epidural opioids upon persistent pain sensitivity in neonatal rat pups. Two models o f persistent pain were used, subcutaneous injection of carrageenan, and top ical application of capsaicin cream, both to the hind paw. The contribution of individual opioid receptor subtypes in the spinal cord to analgesia wer e tested at different developmental stages using epidural mu (morphine sulp hate), delta (DPDPE) and kappa (U69593) opioid receptor agonists in neonata l rats aged P (postnatal day) 3, 10 and 21. Rat pups at all three ages disp layed a reduction in mechanical (von Frey hair) threshold following carrage enan-induced inflammation of the hind paw that was evident at 3 h and was s till present 5 h after application. This effect was greatest in magnitude a t P21. This response was blocked by low doses of all three agonists at all ages, relative effectiveness varying with age. Comparison with potencies in acute tests (Marsh, D., Dickenson, A., Hatch, D. and Fitzgerald, M., Epidu ral opioid analgesia in infant rats I: mechanical and heat responses, Pain 82 (1999) 23-32) show that opioid potency is significantly greater in the p resence of carrageenan inflammation at all ages. Topical capsaicin applicat ion to the hind paw produced a significant fall in withdrawal latencies to noxious heat. Generally, epidural opioid agonists did not block this C-fibr e induced sensitization except at P3, when morphine and DPDPE did prevent t he fall in threshold in a dose dependent manner. The results show that newb orn rat pups are capable of displaying both allodynia and hyperalgesia foll owing experimental inflammation that is blocked by epidural mu, delta and k appa opioids. The opioid potency is enhanced compared with antinociception in acute tests. This is not observed following capsaicin hyperalgesia and i s therefore not a general consequence of C fibre induced increases in centr al excitability but relies upon mechanisms special to inflammatory pain. (C ) 1999 International Association for the Study of Pain. Published by Elsevi er Science B.V.