Effect of insulin hypoglycemic stress on nociceptive responses to mu- and kappa-opioid receptor agonists at LH-surge in female rats.
In a randomized, prospective, controlled and crossover study, the effects of insulin hypoglycemic stress on nociceptive responses to mu- and kappa-opioid receptor directed drugs during steroid-induced preovulatory LH-surge were seen in ovariectomized female rats. Ovariectomized rats were equally distributed in two groups of 10. In group 1 rats, LH-surge was induced by sequential treatment with estradiol benzoate 7.5 micro g/rat s.c. and progesterone 5 mg/rat s.c., whereas in group 2 rats, vehicles of estradiol benzoate and progesterone were given in a sequential manner. A third group consisted of sham-operated rats, which received no treatment. Rats were exposed to insulin-induced hypoglycemic stress 1 h before the peak of LH-surge. Antinociceptive responses of morphine, buprenorphine and pentazocine were observed at peak LH-surge during hypoglycemic stress. Increased nociceptive responses to noxious stimulus and decreased percent maximal possible effect for morphine, buprenorphine and pentazocine at LH-surge were significantly (p < 0.01) reversed during insulin hypoglycemic stress. There was a significant (p < 0.01) decrease in the ED(50) values of morphine, buprenorphine and pentazocine during hypoglycemic stress. The present study indicates that insulin hypoglycemic stress is responsible for increased antinociceptive activities of morphine, buprenorphine and pentazocine and decreased sensitivity to noxious stimulus in ovariectomized rats with or without steroid-induced LH-surge.
Srivastava
R K
RK
Department of Pharmacology, Pt. B.D. Sharma Post Graduate Institute of Medical Sciences, Haryana, India. savi_verma@rediffmail.com
Verma
S
S
Tandon
M
M
D000701:Analgesics, Opioid / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D002047:Buprenorphine / Q000008:administration & dosage; D018592:Cross-Over Studies; D005260:Female; D007003:Hypoglycemia / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*; D007328:Insulin / Q000633:toxicity*; D007986:Luteinizing Hormone / Q000097:blood*; D009020:Morphine / Q000008:administration & dosage; D010052:Ovariectomy; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods; D010423:Pentazocine / Q000008:administration & dosage; D011446:Prospective Studies; D051381:Rats; D017207:Rats, Sprague-Dawley; D017473:Receptors, Opioid, kappa / Q000819:agonists* / Q000502:physiology; D017450:Receptors, Opioid, mu / Q000819:agonists* / Q000502:physiology; D013312:Stress, Physiological / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*
D000701:Analgesics, Opioid; D007328:Insulin; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D002047:Buprenorphine; D009020:Morphine; D007986:Luteinizing Hormone; D010423:Pentazocine