Pharmacological characterisation of the rat brachial plexus avulsion model of neuropathic pain.
Recently, our laboratory has proposed the avulsion of rat brachial plexus as a new and reliable model for the study of neuropathic pain. In this model, the neuropathy can be detected even at distant sites from the injury, both in ipsilateral and contralateral hindpaws. The purpose of this study was to pharmacologically characterise this behavioural model of persistent peripheral neuropathic pain by assessing the effects of several analgesic drugs currently used in clinical practice. For this purpose, the effects of these drugs on the mechanical and cold allodynia were analysed 20-40 days after rat brachial plexus avulsion. Injection of saline, administered by the same route as the other drugs, did not significantly affect the nociceptive threshold either in sham-operated or in neuropathic rats. However, administration of the opioid analgesic morphine (5 mg/kg, s.c.), the alpha2 adrenoceptor agonist clonidine (300 microg/kg, i.p.), the NMDA receptor antagonist ketamine (25 mg/kg, i.p.) or the anticonvulsant drug gabapentin (70 mg/kg, p.o.) consistently reduced both mechanical and cold allodynia following avulsion of rat brachial plexus. The administration of the selective COX-2 inhibitor celecoxib (10 mg/kg, p.o.) blocked mechanical allodynia, but not cold allodynia, whereas the sodium channel blocker lidocaine (40 mg/kg, i.p.) attenuated only cold allodynia. The non-steroidal anti-inflammatory drug diclofenac (100 mg/kg, i.p.), the steroidal anti-inflammatory dexamethasone (1.5 mg/kg, i.p.) and the antidepressant imipramine (10 mg/kg, i.p.) all failed to significantly attenuate both mechanical and cold allodynia in the rats following avulsion of brachial plexus. These findings suggest that avulsion-associated mechanical and cold allodynia, two classic signs of persistent neuropathic pain, were consistently prevented by several analgesics currently available in clinical practice, namely morphine, clonidine, ketamine and gabapentin, and to a lesser extent by celecoxib and lidocaine. Therefore, this new proposed model of persistent nociception seems to be suitable for the study of the underlying mechanisms involved in neuropathic pain and for the identification of potential clinically relevant drugs to treat this aspect of peripheral neuropathy.
Department of Pharmacology, Centre of Biological Sciences, Universidade Federal de Santa Catarina, Rua Ferreira Lima 82, Florianópolis, SC 88015-420, Brazil.
Rubens
R
Rodrigues-Filho
Maria Martha
MM
Campos
Juliano
J
Ferreira
Adair R S
AR
Santos
Jayme A
JA
Bertelli
João B
JB
Calixto
D000085:Acetates / Q000627:therapeutic use; D000588:Amines; D000700:Analgesics / Q000627:therapeutic use*; D000704:Analysis of Variance; D000818:Animals; D001917:Brachial Plexus / Q000187:drug effects / Q000293:injuries / Q000503:physiopathology*; D020516:Brachial Plexus Neuropathies / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D000068579:Celecoxib; D003000:Clonidine / Q000627:therapeutic use; D003509:Cyclohexanecarboxylic Acids; D004195:Disease Models, Animal; D000077206:Gabapentin; D007649:Ketamine / Q000627:therapeutic use; D008012:Lidocaine / Q000627:therapeutic use; D008297:Male; D009020:Morphine / Q000627:therapeutic use; D009437:Neuralgia / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D009619:Nociceptors / Q000187:drug effects*; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects*; D011720:Pyrazoles; D011843:Radiculopathy / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides / Q000627:therapeutic use; D005680:gamma-Aminobutyric Acid
D000085:Acetates; D000588:Amines; D000700:Analgesics; D003509:Cyclohexanecarboxylic Acids; D011720:Pyrazoles; D013449:Sulfonamides; D005680:gamma-Aminobutyric Acid; D007649:Ketamine; D000077206:Gabapentin; D009020:Morphine; D008012:Lidocaine; D000068579:Celecoxib; D003000:Clonidine