Analgesia opioids producing

All opioids produce their effect by activating one or more of the three types of receptors. Thus analgesia involves the activation of the mu receptors that are located mainly at supraspinal sites and kappa receptors in the spinal cord delta receptors may also be involved but their relative contribution is unclear. Nevertheless, the actions of the opioids on these receptors is complex, as there is evidence that the same substance may act as a full agonist, or as an antagonist at different sites within the brain. 

The antinociceptive effects of mu opioid agonists within the RVM require activation of a class of neurons termed off-cells that exert a net inhibitory effect on nociception [4-6], Mu opioid activation of off-cells is indirect, and triggered by disinhibition. In addition to the indirect activation of off-cells, mu opioids inhibit another class of neurons in RVM, termed on-cells. This inhibition is direct, but suppression of on-cell discharge is not sufficient to produce behavioral analgesia. Opioid inhibition of on-cells may however assume an important role in inflammatory pain states, in which these neurons likely contribute to hyperalgesia [7]. 

The opioids produce analgesia by binding to various opioid receptors in the brain, brainstem, and spinal cord, thus mimicking the effects of endogenous opioid peptides (endorphins). Opioids appear to affect both the sensation of noxious stimulation (pain) and the emotional component of subjective distress (suffering). 

Gear RW, Miaskowski C, Gordon NC, Paul SM, Heller PH, Levine JD. Kappa-opioids produce significantly greater analgesia in women than in men. Nat Med 1996 2 1248-50. 

In a double-blind, placebo-controUed study in 24 elderly patients scheduled for elective total hip replacement who were randomized to either intrathecal morphine 160 pg or nalbuphine 400 pg postoperatively, when the pain score was greater than 3 cm on a visual analogue scale, nalbuphine produced significantly faster onset and shorter duration of analgesia (5). Both opioids produced adequate maximal pain rehef in aU patients. The adverse effects profile was umemarkable in both groups. 

Opioids produce analgesia without loss of consciousness, although drowsiness, changes in mood, and mental clouding occur. Responses to painful stimuh are blocked at several locations in the brain, resulting in both an alteration in the sensation of pain and a change in the affective response. The ability of a patient to perceive pain can remain the same while tolerance to pain is markedly increased (29). 

Whereas opioids are used primarily for analgesia, they produce a host of other effects, as summarized below. High doses of opioids can produce muscular rigidity in humans. Chest wall rigidity severe enough to compromise respiration is not uncommon during anesthesia with fentanyl, alfen-tanil, remifentanil, and sufentanil. 

UNTOWARD EFFECTS AND PRECAUTIONS Morphine and related opioids produce a wide spectrum of unwanted effects, including respiratory depression, nausea, vomiting, dizziness, mental clouding, dysphoria, pruritus, constipation, increased pressure in the biliary tract, urinary retention, hypotension, and rarely dehiium. Increased sensitivity to pain after analgesia has worn off also may occur. 

Opioid-induced analgesia is produced through the action of opioid receptors on presynaptic terminals of the C-fibers and A-delta fibers. These fibers, which transmit nociceptive messages, are inhibited by the indirect effects of opioids, which in turn reduce the release of neurotransmitters such as substance P, CGRP, and glutamate. This effect occurs in the peripheral nervous system as well as at the primary afferent terminals in the spinal cord. 

Morphine and other opioids produce analgesia in part releasing acetylcholine and stimulating nAChRs. Nicotine stimulates the same nAChRs. 

The best-understood sites of action of morphine are at spinal and brainstem/ midbrain loci, producing both the wanted and unwanted effects of the opioid. The spinal actions of opioids and their mechanisms of analgesia involve (1) reduced transmitter release from nociceptive C-fibres so that spinal neurons are less excited by incoming painful messages, and (2) postsynaptic inhibitions of neurons conveying information from the spinal cord to the brain. This dual action of opioids can result in a... 

This class produces analgesia and has a ceiling effect on respiratory depression and lower abuse potential than morphine. However, psychotomimetic responses (e.g., hallucinations and dysphoria with pentazocine), a ceiling analgesic effect, and the propensity to initiate withdrawal in opioid-dependent patients have limited their widespread use. 

Although cannabinoids interact with opioids in analgesia, there also appear to be opioid-independent mechanisms (Hamann and di Vadi 1999). The analgesia produced by cannabinoids alone is not abolished by pretreatment with the general opioid antagonist naloxone (Gilbert 1981 Welch and Stevens 1992 Ferri et al. 1986). 

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