Effects of morphine on visceral nociception evoked by colorectal distension in rats: comparative examinations of electrophysiological and behavioral responses.

The purpose of this study was to compare the effects of intravenously administered morphine on electrophysiological and behavioral responses to colorectal distension (CRD) and to examine the influence of noxious stimuli applied to another part of the body (a laminectomy) on the visceromotor response to CRD. The effects of morphine (0.1-6.4 mg·kg-1) were examined in rate anesthetized with pentobarbital. Electrophysiological (n=16) and behavioral experiments (n=47) were done. Electrophysiological experiments were conducted to examine the effects of morphine on the responses of visceral dorsal horn neurons to CRD; behavioral studies were conducted to compare the effects of morphine with and without a laminectomy (intact group:n=24; laminectomy group:n=23). Morphine suppressed the evoked activities of the visceral dorsal horn neurons in a dose-dependent manner. Similar suppression of the behavioral visceromotor response was observed. Visceromotor thresholds were significantly lower in the intact group than in the laminectomy group during the control study. When morphine was administered, the visceromotor thresholds in both groups increased to a similar level. Behavioral and neurophysiological responses to CRD were suppressed in a similar fashion by morphine. Although laminectomy affected the threshold values of CRD for visceromotor responses, the laminectomy per se plays an insignificant role when adequate morphine is administered.

Lack of opiate effects on cat C polymodal nociceptive fibers.

The direct application of preservative-free morphine sulfate (1.5%, 1 ml, 19.8 mumol) or fentanyl (0.06%, 1 ml, 1.07 mumol) on the superficial radial or saphenous nerve of cats did not alter the response of single C polymodal nociceptive fibers (PMNs) to noxious radiant heat stimulation of their peripheral receptive fields. Intravenous administration of fentanyl (100 or 200 micrograms/kg, 0.179 or 0.358 mumol/kg) also showed a similar lack of effect on the radiant heat evoked responses of single PMNs. Slight changes in the mean latencies following drug administration were recognized, which were not statistically significant. The use of morphine (1.5%, 1 ml, 19.8 mumol) with preservatives (chlorbutanol 0.5% and sodium bisulfite less than 0.1%) caused conduction block of PMNs within 6-15 min. Subsequent washout of the drug resulted in the return of the unitary discharges within 8 min. Lidocaine (0.25 and 0.5%, 10.7 mumol and 21.4 mumol) caused conduction block within 5-18 min. These data support the classically held concept that opiates, in clinically useful concentrations, do not alter peripheral nerve function.

Inhibition of nociceptive neuronal responses in the cat's spinal dorsal horn by electrical stimulation and morphine microinjection in nucleus raphe magnus.

The descending inhibitions produced by morphine microinjection and electrical stimulation in the nucleus raphe magnus (NRM) on dorsal horn neurons excited by noxious heating of the skin and/or electrical stimulation of hind limb nerves were examined in the cat. The responses to A-volleys were inhibited to 60.1% (mean, n = 9), those to C-volleys to 64.8% of control (mean, n = 6) and responses to skin heating to 25.3% (mean, n = 8) by electrical NRM stimulation. Morphine (e.g., 10 or 20 micrograms) microinjected into the NRM markedly reduced the responses elicited by afferent C-fiber stimulation (mean 55.6%, n = 8) and the responses to noxious skin heating (mean 38.1%, n = 8), while responses to A-volleys in hind limb nerves were less attenuated (mean 73.6%, n = 8). The effects of morphine were partially or completely blocked by microinjection (10 micrograms) of naloxone into the NRM. It is concluded that morphine microinjection into the NRM generates descending inhibition on the transmission of nociceptive information in the dorsal horn of the spinal cord. This may partly explain the mechanisms of morphine analgesia.