Mechanism of antinociceptive effect of nimodipine in experimental diabetic neuropathic pain.
This study used streptozotocin-(STZ; 50 mg/kg, i.v.) diabetic rats and monitored the weekly thermal nociceptive thresholds for 8-week diabetes. Nimodipine (10 mg/kg i.p.) treatment initiated after 8 weeks of diabetes antagonized the hyperalgesic response in diabetic rats. However, insulin treatment showed a partial response in these animals. Thermal hyperalgesia showed reduced sensitivity to the antinociceptive effect of morphine (5 mg/kg, i.p.). Furthermore, a reduced sensitivity to the antinociceptive effect of baclofen (GABAB agonist; 4 mg/kg i.p.) was observed. Five days of treatment with MK-801 (N-methyl-D-aspartate [NMDA] receptor antagonist 0.5 mg/kg i.p.) completely reversed 8-week diabetes-induced thermal hyperalgesia. These data suggest that diabetes-induced hyperalgesia may be the consequence of increased excitatory tone within the spinal cord. An increased release of glutamate and activation of the NMDA receptor would maintain the hyperalgesic state. Reduced activity of both opioidergic and GABAB ergic inhibitory systems might accelerate the increased excitation, thus contributing to the ongoing pain in diabetic rats.
Gupta
M
M
Department of Pharmacology, Post Graduate Institute of Medical Sciences, Rohtak, India. monicag@rediffmail.com
Singh
J
J
Sood
S
S
Arora
B
B
D000700:Analgesics / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D003929:Diabetic Neuropathies / Q000188:drug therapy*; D005260:Female; D008297:Male; D009553:Nimodipine / Q000494:pharmacology / Q000627:therapeutic use*; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats
D000700:Analgesics; D009553:Nimodipine