Treatment of Pain

FIGURE 14-3 Putative mechanism of opioid action on peripheral nerve terminals. See text for discussion. 

Consistent with these hypotheses is the finding that continuous infusion of the opioid into the epidural or intrathecal space provides optimal pain relief postoper-atively or in chronic, intractable pain.2 40 83 Continuous infusion is associated with certain side effects, especially nausea and constipation, as well as the potential for disruption of the drug delivery system.24 57 77 Problems with tolerance have also been reported during continuous administration,27 but it is somewhat controversial whether tolerance really develops when these drugs are used appropriately in the clinical management of pain (see section on Concepts of Addiction, Tolerance, and Physical Dependence ). Hence, the benefit-to-risk ratio for continuous epidural or intrathecal infusion is often acceptable in patients with severe pain. This method of opioid administration continues to gain acceptance.24 57 

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Inhibition of the metabolism of extracellular adenosine or its uptake proteins is being explored for therapeutic purposes. AK inhibitors have been proposed for the treatment of pain and seizures however, the promising clinical development of these efficacious compounds was discontinued due to toxicity. 

The dosage of acetylsalicylic acid in the treatment of pain and fever is 1.5-3 g daily and in the prophylaxis of heart attacks 30-100 mg daily. 

Dorfman D, Dalton A et al (1999) Treatment of painful distal sensory polyneuropathy in HIV-infected patients with a topical agent results of an open-label trial of 5% lidocaine gel. AIDS 13(12) 1589-1590... 

The dimethylheptyl side-chain analogue of 9-carboxy-A -THC, ajulemic acid, CT-3, (166) is currently in clinical development for treatment of pain and inflammation [121, 122]. Compound (166) does show some affinity for CBi and CB2 receptors, but may also exert anti-inflammatory and analgesic effects through other mechanisms. It does not appear to be psychoactive in humans [123]. 

Acetaminophen generally is considered the drug of choice for the treatment of pain during pregnancy (Table 44—5). If... 

Owing to the lag time between initiation and effect, capsaicin is not used for treatment of acute pain from injury. Instead, topical capsaicin is used for chronic pain from musculoskeletal and neuropathic disorders. Capsaicin preparations have been studied in the treatment of pain from diabetic neuropathy, osteoarthritis, rheumatoid arthritis, postherpetic neuralgia, and other disorders.48 It is often used as an adjuvant to systemic analgesics in these chronic pain conditions. 

In 2001 two Danish researchers, Asbjorn Hrobjartsson and Peter Gotzsche, published an influential meta-analysis in which they estimated the difference between the effects of getting a placebo versus doing nothing at all.14 Although they found a significant placebo effect, especially in the treatment of pain, the overall effect seemed very small - much smaller than would have been expected of a powerful treatment. On the basis of these data, the researchers asked Is the placebo powerless and answered their own question by concluding that there was little evidence that placebos have powerful clinical effects. 

Substituted 3,4-dihydropyrimido[l,2- ]pyrimidines and the benzologues 3,4-dihydropyrimido[l,2- ]quinazolines have opiate and NMDA receptor inhibitory activity and have been claimed for treatment of pain and urinary incontinence <2002W0030934>. 

Opium and its derivatives have been employed for centuries for the treatment of pain. Morphine was first synthesized in 1805 and has proven to be one of the most effective analgesic agents available [1], Morphine and its analogs are particularly useful because they diminish pain sensation while maintaining consciousness. However, opiates induce severe side-effects including respiratory depression, nausea, bradycardia and constipation and long-term use of opiates can cause addiction [2]. 

Direct measures (e.g., treatment of pain, hypovolemia, fever, infection, or salicylate overdose) can be effective. A rebreathing device (e.g., paper bag) can help control hyperventilation. 

In addition to treating MDD [51-53], duloxetine was approved as the first agent for the treatment of painful diabetic neuropathy in the U.S. [54-56]. It also has been used for stress urinary incontinence in women in Europe [57,58]. In 2007, duloxetine was approved for the treatment of generalized anxiety disorder in the U.S. 

The FDA approved this selective cyclooxigenase (COX)-2 inhibitor (Vioxx) for the treatment of pain and inflammation in 1999. This NSAID demonstrated to have a lower risk of side effects such as gastrointestinal ulcers and bleeding than nonse-lective COX inhibitors, for example, ibuprofen. In 2004, a long-term study of Vioxx in patients at increased risk of colon polyps was halted because of an increased cardiovascular risk (heart attack, stroke) in the rofecoxib group. Subsequently, Merck withdrew the drug from the world market at the end of September 2004 [46]. 

Dermal Effects. No reports are available on the toxicity of chloroform to skin after inhalation and oral exposures in humans. Stratum comeum damage was reported after a topical exposure of chloroform of 15 minutes duration for 6 consecutive days (Malten et al. 1968). Chloroform was used as a vehicle for the topical application of aspirin for the treatment of painful herpes zoster lesions in male and female humans. The only reported side-effect was an occasional burning sensation to the skin as the chloroform evaporated after application (King 1993). 

Centrally acting muscle relaxants (A) lower muscle tone by augmenting the activity of intraspinal inhibitory interneurons. They are used in the treatment of painful muscle spasms, e.g., in Ltillmann, Color Atlas of Pharmacology 2000 Thieme All rights reserved. Usage subject to terms and conditions of license. 

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