Local administration of mu or kappa opioid agonists attenuates capsaicin-induced thermal hyperalgesia via peripheral opioid receptors in rats.
BACKGROUND
By acting on peripheral opioid receptors, opioid agonists can attenuate nociceptive responses induced by a variety of agents.


OBJECTIVE
This study was conducted to characterize capsaicin-induced thermal hyperalgesia in rats and to evaluate the hypothesis that local administration of either mu or kappa opioid agonists (fentanyl and U50,488, respectively) can attenuate capsaicin-induced nociception.


METHODS
Capsaicin was administered s. c. in the tail of rats to evoke a nociceptive response, which was measured by the warm-water tail-withdrawal procedure. Either fentanyl or U50,488 was co-administered with capsaicin in the tail to evaluate local antinociceptive effects. In addition, the local antagonism study was performed to confirm the site of action of both opioid agonists.


RESULTS
Capsaicin (0.3-10 microg) dose dependently produced thermal hyperalgesia manifested as reduced tail-withdrawal latencies in 45 degrees C water. Co-administration of either fentanyl (0.32-3.2 microg) or U50,488 (10-100 microg) with capsaicin (3 microg) attenuated capsaicin-induced hyperalgesia in a dose-dependent manner. Furthermore, this local antinociception was antagonized by small doses (10-100 microg) of an opioid antagonist, quadazocine, applied s.c. in the tail. However, the locally effective doses of quadazocine, when applied s.c. in the back (i.e., around the scapular region), did not antagonize either fentanyl or U50,488.


CONCLUSIONS
In this experimental pain model, activation of peripheral mu or kappa opioid receptors can attenuate capsaicin-induced thermal hyperalgesia in rats. It supports the notion that peripheral antinociception can be achieved by local administration of analgesics into the injured tissue without producing central side effects.
Ko
M C
MC
Department of Pharmacology, University of Michigan Medical School, 1301 MSRB III, Ann Arbor, MI 48109-0632, USA.
Tuchman
J E
JE
Johnson
M D
MD
Wiesenauer
K
K
Woods
J H
JH
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000008:administration & dosage; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000037:antagonists & inhibitors; D000772:Anesthesia, Local; D000818:Animals; D001392:Azocines / Q000008:administration & dosage; D002211:Capsaicin; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005283:Fentanyl / Q000008:administration & dosage / Q000037:antagonists & inhibitors; D006358:Hot Temperature / Q000009:adverse effects; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy*; D007279:Injections, Subcutaneous; D008297:Male; D009292:Narcotic Antagonists / Q000008:administration & dosage; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy*; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017473:Receptors, Opioid, kappa / Q000819:agonists*; D017450:Receptors, Opioid, mu / Q000819:agonists*
D018712:Analgesics, Non-Narcotic; D000701:Analgesics, Opioid; D001392:Azocines; D009292:Narcotic Antagonists; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D002211:Capsaicin; D005283:Fentanyl; C035969:quadazocine