Possible mechanisms of insulin antinociception.

The antinociceptive mechanisms of insulin are not clearly understood. It has been postulated that insulin may act as a neuromodulator. The present study investigates the possible mechanisms of insulin antinociception in mice using the tail flick test. Healthy Swiss male albino mice were treated with insulin and the antinociceptive effect of modulators of 5-HT, NMDA, dopamine, opioids, potassium and calcium channels was tested, followed by blood sugar estimation. All drug doses were given as milligrams per kilogram of body weight 30 min prior to insulin administration, except for para-chlorophenylanine (pCPA), which was given for three consecutive days per orally. Pretreatment with morphine (opioid agonist), 5-Hydroxytryptophan (5-HTP; 5-HT precursor), nicorandil (K(+) channel opener) and nimodipine (Ca(+) channel antagonist) significantly (p < 0.001) potentiated insulin antinociception, whereas naloxone (opioid antagonist), ketanserin (5-HT(2) receptor antagonist), pCPA (5-HT depleter), ondansetron (5-HT(3) receptor antagonist), L-dopa (dopamine precursor), reserpine (dopamine depleter), ketamine (NMDA receptor antagonist) and glibenclamide (K(+) channel blocker) significantly antagonized insulin antinociception (p < 0.001). Results suggest that 5-HT, dopamine, NMDA, opioidergic receptors and potassium and calcium channels play a significant role in insulin analgesia. However, detailed studies on individual mechanisms are necessary. (c) 2004 Prous Science. All rights reserved.