Mu and delta, but not kappa, opioid agonists induce spastic paraparesis after a short period of spinal cord ischaemia in rats.
BACKGROUND
Intrathecal (IT) morphine given after a short interval of aortic occlusion in a rodent model induced transient spastic paraparesis via opioid receptor-predicted actions in spinal cord. To determine the role(s) of spinal opioid receptor subtypes we investigated whether IT administration of various selective opioid receptor agonists can induce paraparesis following a short period of spinal cord ischaemia in rats.


METHODS
In Sprague-Dawley rats implanted with an IT catheter, spinal cord ischaemia was induced for 6 min using an intraaortic balloon. Mu ([D-Ala2, N-Me Phe4, Gly-ol5] enkephalin), kappa (U50488H) or delta ([D-Pen(2,5)] enkephalin) selective agonists were injected intrathecally 30 min after reperfusion. A separate group of animals was used to investigate the dose-response effect on this motor dysfunction. For this purpose, three doses of mu, kappa, or delta agonists were injected intrathecally after ischaemia. After IT injection, recovery of motor function was assessed periodically using the motor deficit index (0=complete recovery; 6=complete paraplegia).


RESULTS
IT administration of mu and delta but not kappa agonists produced dose-dependent effects in the induction of spastic paraparesis. In addition, this spasticity induced by IT mu and delta agonists was reversed completely by IT naloxone and naltrindole, respectively.


CONCLUSIONS
These results suggest that the effect of various opioids on motor function after a short period of spinal cord ischaemia depends upon individual opioid receptor subtypes.
Kakinohana
M
M
Department of Anesthesiology, Faculty of Medicine, University of the Ryukyus, Okinawa, Japan. mnb-shk@ryukyu.ne.jp
Nakamura
S
S
Fuchigami
T
T
Davison
K J
KJ
Marsala
M
M
Sugahara
K
K
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology; D018712:Analgesics, Non-Narcotic / Q000633:toxicity; D000701:Analgesics, Opioid / Q000633:toxicity*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D020881:Enkephalin, D-Penicillamine (2,5)- / Q000494:pharmacology; D007278:Injections, Spinal; D008297:Male; D009068:Movement / Q000187:drug effects; D020336:Paraparesis, Spastic / Q000139:chemically induced* / Q000209:etiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017465:Receptors, Opioid, delta / Q000819:agonists* / Q000502:physiology; D017473:Receptors, Opioid, kappa / Q000819:agonists / Q000502:physiology; D017450:Receptors, Opioid, mu / Q000819:agonists* / Q000502:physiology; D020760:Spinal Cord Ischemia / Q000150:complications* / Q000473:pathology
D018712:Analgesics, Non-Narcotic; D000701:Analgesics, Opioid; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D020881:Enkephalin, D-Penicillamine (2,5)-