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 of persistent pain were used, subcutaneous injection of carrageenan, and topical application of capsaicin cream, both to the hind paw. The contribution of individual opioid receptor subtypes in the spinal cord to analgesia were tested at different developmental stages using epidural mu (morphine sulphate), delta (DPDPE) and kappa (U69593) opioid receptor agonists in neonatal rats aged P (postnatal day) 3, 10 and 21. Rat pups at all three ages displayed a reduction in mechanical (von Frey hair) threshold following carrageenan-induced inflammation of the hind paw that was evident at 3 h and was still present 5 h after application. This effect was greatest in magnitude at 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., Epidural opioid analgesia in infant rats I: mechanical and heat responses, Pain 82 (1999) 23-32) show that opioid potency is significantly greater in the presence of carrageenan inflammation at all ages. Topical capsaicin application to the hind paw produced a significant fall in withdrawal latencies to noxious heat. Generally, epidural opioid agonists did not block this C-fibre induced sensitization except at P3, when morphine and DPDPE did prevent the fall in threshold in a dose dependent manner. The results show that newborn rat pups are capable of displaying both allodynia and hyperalgesia following experimental inflammation that is blocked by epidural mu, delta and kappa opioids. The opioid potency is enhanced compared with antinociception in acute tests. This is not observed following capsaicin hyperalgesia and is therefore not a general consequence of C fibre induced increases in central excitability but relies upon mechanisms special to inflammatory pain.
Marsh
Deborah
D
Department of Anatomy and Developmental Biology, University College London, Gower Street, London WC1E 6BT, UK Department of Pharmacology, University College London, London WC1E 6BT, UK Department of Anaesthesia, Institute of Child Heath, London WC1N 1EH, UK.
Dickenson
Anthony
A
Hatch
David
D
Fitzgerald
Maria
M
D015360:Analgesia, Epidural / Q000379:methods*; D000701:Analgesics, Opioid / Q000627:therapeutic use*; D000818:Animals; D000831:Animals, Newborn; D044482:Benzeneacetamides; D002211:Capsaicin / Q000037:antagonists & inhibitors*; D002351:Carrageenan / Q000037:antagonists & inhibitors*; D004353:Drug Evaluation, Preclinical; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000627:therapeutic use; D005260:Female; D007279:Injections, Subcutaneous; D008297:Male; D009020:Morphine / Q000627:therapeutic use; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy*; D011759:Pyrrolidines / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D017465:Receptors, Opioid, delta / Q000819:agonists; D017473:Receptors, Opioid, kappa / Q000819:agonists; D017450:Receptors, Opioid, mu / Q000819:agonists
D000701:Analgesics, Opioid; D044482:Benzeneacetamides; D004745:Enkephalins; D011759:Pyrrolidines; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D009020:Morphine; D020881:Enkephalin, D-Penicillamine (2,5)-; D002351:Carrageenan; C045444:U 69593; D002211:Capsaicin