Pre-emptive administration of clonidine prevents development of hyperalgesia to mechanical stimuli in a model of mononeuropathy in the rat.
Traumatic nerve injury in man can often result in the development of neuropathy. An animal model of neuropathic hyperalgesia is produced by loose ligation of the sciatic nerve in the rat. We have examined the effect of pre-emptive treatment with a number of drugs on the development of hyperalgesia in this model. Animals received clonidine (1 mg.kg-1, s.c.), morphine (5 mg.kg-1, s.c.), (+/-)-baclofen (40 mg.kg-1, s.c.), carbamazepine (50 mg.kg-1, s.c.) or vehicle (4 ml.kg-1, s.c.) 30 min prior to loose ligation or sham-operation. Morphine- and clonidine-treated animals were administered a second dose of drug 6h following surgery. Twenty-six or twenty-nine days following surgery, the ipsilateral (ipsi.) and contralateral (contra.) paw withdrawal thresholds were determined using an Algesymeter. In vehicle-treated animals the ipsilateral paw withdrawal threshold (118 +/- 7 g) was significantly lower (P < 0.0001, paired t-test) than the contralateral (195 +/- 7 g). In contrast, in animals pre-treated with clonidine no significant difference between ipsilateral (200 +/- 9 g) and contralateral (191 +/- 7 g) paw withdrawal thresholds was detected. Morphine pre-treatment was less effective in preventing development of hyperalgesia; however, whilst the ipsilateral (146 +/- 18 g) paw withdrawal threshold tended to be lower than the contralateral (183 +/- 8 g), this was not significant.(ABSTRACT TRUNCATED AT 250 WORDS)
Smith
G D
GD
Department of Gastrointestinal Pharmacology, Glaxo Group Research, Ware, Herts, UK.
Harrison
S M
SM
Wiseman
J
J
Elliott
P J
PJ
Birch
P J
PJ
D000704:Analysis of Variance; D000818:Animals; D001418:Baclofen / Q000008:administration & dosage / Q000494:pharmacology; D002220:Carbamazepine / Q000008:administration & dosage / Q000494:pharmacology; D003000:Clonidine / Q000008:administration & dosage / Q000627:therapeutic use*; D004195:Disease Models, Animal; D006930:Hyperalgesia / Q000517:prevention & control*; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology; D010523:Peripheral Nervous System Diseases / Q000188:drug therapy / Q000503:physiopathology*; D010812:Physical Stimulation; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D012584:Sciatic Nerve / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology*; D013997:Time Factors
D002220:Carbamazepine; D009020:Morphine; D001418:Baclofen; D003000:Clonidine