NEUROPHYSIOLOGIC EFFECTS OF OPIOIDS

Analgesic Action of Opioids

In human beings, morphine-like drugs produce analgesia, drowsiness, changes in mood, and mental clouding. A significant feature of opioid analgesia is that it is not associated with loss of consciousness. When morphine in the same dose is given to a normal, pain-free individual, the experience may be unpleasant. The relief of pain by morphine-like opioids is relatively selective, in that other sensory modalities are not affected. Patients frequently report that the pain is still present, but that they feel more comfortable. It is also important to distinguish between pain caused by stimulation of nociceptive receptors and transmitted over intact neural pathways (nociceptive pain) and pain that is caused by damage to neural structures, often involving neural supersensitivity (neuropathic pain). Although nociceptive pain usually is responsive to opioid analgesics, neuropathic pain typically responds poorly to opioid analgesics and may require higher doses of drug.^[48] Not only is the sensation of pain altered by opioid analgesics, but the affective response is changed as well. It is clear, however, that alteration of the emotional reaction to painful stimuli is not the sole mechanism of analgesia. Intrathecal or epidural administration of opioids can produce profound segmental analgesia without causing significant alteration of motor or sensory function or subjective effects. ^[49]

The level of antinociception produced by an opioid is determined by the intensity of the nociceptive stimulus and the intrinsic efficacy of the opioid. When opioids are given in combination, the effects can only be predicted on the basis of the nociception when the drugs are administered alone.^[50] It has been shown that opioid antinociceptive effects are enhanced in animal models of inflammation. Recently it was shown that the sensitization to opioids is related to a central rather than peripheral site of action.^[51]

Animal and human studies indicate the existence of sex-related differences in opioid-mediated behavior.^[52] Sarton and associates examined the influence of morphine on experimentally induced pain in healthy volunteers, and demonstrated sex differences in morphine analgesia, with greater morphine potency but slower speed of onset and offset in women.^[53] The mechanism of the sex differences remains to be clarified.

Controversies remain about the analgesia produced by peripheral actions of opioids. A recent review concluded from metaanalysis that intraarticularly administered morphine has a definite but mild analgesic effect.^[54] It may be dose dependent, and a systemic effect cannot be completely excluded. Addition of opioids in brachial plexus block has been reported to improve success rate and postoperative analgesia.^{[55] [56]} In contrast, in another study, addition of sufentanil did not prolong the duration of brachial plexus block.^[57] Because of its local anesthetic effect on peripheral nerves, meperidine was tested for intravenous regional anesthesia. However, it was demonstrated that doses of meperidine large enough to produce effective postoperative analgesia caused a significant incidence of side effects.^[58]