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the brain via peripheral nerves. Visceral pain results from activation of specific pain receptors in the intestine (visceral nociceptive receptors); it is characterized as a deep aching or cramping sensation, but its source is often experienced at sites remote from the site of receptor activation, a phenomenon known as referred pain. Neuropathic pain results from injury to peripheral receptors, nerves, or the central nervous system; it is typically burning, the skin feels abnormally unpleasant when gently touched (dysesthesia), and it often occurs in an area of sensory loss, as in the case of postherpetic neuralgia (shingles).
All of the currently available analgesic (pain-relieving) drugs have limited efficacy for some types of pain. Some are limited by dose-related side effects and some by the development of tolerance or dependence. A cannabinoid, or other analgesic, could potentially be useful under any of the following circumstances:
· There is a medical condition for which it is more effective than any currently available medication.
· It has a broad clinical spectrum of efficacy and a unique side effect profile.
· It has synergistic interactions with other analgesics.
· It exhibits "side effects" that are considered useful in some clinical situations.
· Its efficacy is enhanced in patients who have developed tolerance to opioids.
There have not been extensive clinical studies of the analgesic potency of cannabinoids, but the available data from animal studies indicate that cannabinoids could be useful analgesics. In general, cannabinoids seem to be mild to moderate analgesics. Opiates, such as morphine and codeine, are the most widely used drugs for the treatment of acute pain, but they are not consistently effective in chronic pain; they often induce nausea and sedation, and tolerance occurs in some patients. Recent research has made it clear that CB1 receptor agonists act on pathways that partially overlap with those activated by opioids but through pharmacologically distinct mechanisms (see chapter 2). Therefore, they would probably have a different side effect profile and perhaps additive or synergistic analgesic efficacy.
In light of the evidence that cannabinoids can reduce pain in animals, it is important to re-evaluate the evidence of analgesic efficacy in humans and to ask what clinical evidence is needed to decide whether cannabinoids have any use in the treatment of pain.