Pain, postherpetic neuralgia

Finally, local anesthetics can be administered via a transdermal patch.1 In particular, transdermal patches containing 5% lidocaine have been used to treat localized pain in musculoskeletal conditions (osteoarthritis, low back pain, myofascial pain)22,25,26 and various types of neuropathic pain (postherpetic neuralgia, diabetic neuropathy).2,24,58 As indicated in Chapter 2, transdermal patches provide a convenient and predictable method for administering drugs to a given anatomical site, and lidocaine patches are now being used to provide symptomatic relief in many conditions involving fairly localized pain. 

Cancer-related pain Postherpetic neuralgia Diabetic neuropathy Low back pain... 

Local and spinal anesthetic also used for treatment of status epilepticus migraine and cluster headaches ventricular arrhythmias, ventricular fibrillation cardiac arrest neuropathic pain, postherpetic neuralgia... 

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. 

An excellent example for an enzymatic resolution process is reported for production of Pregabalin. This drug was approved by the US Food and Drug Administration (FDA) in 2004 against neurophatic pain associated with diabetic peripheral neuropathy and postherpetic neuralgia. Several different routes have been developed based on asymmetric hydrogenation, crystallization and biocatalytic resolutions [16-20]. The most powerful and currently applied process is based on a lipase resolution, shown in Figure 14.3. This process is one of the very few... 

Neuropathic and functional pain is often described in terms of chronic pain. Neuropathic pain (e.g., postherpetic neuralgia, diabetic neuropathy) is a result of nerve damage, but functional pain (e.g., fibromyalgia, irritable bowel syndrome, tension-type headache) refers to abnormal operation of the nervous system. Pain circuits may rewire themselves and produce spontaneous nerve stimulation. 

King RB. 1993. Topical aspirin in chloroform and the relief of pain due to herpes zoster and postherpetic neuralgia. Arch Neurol 50 1046-1053. 

Neuroanatomically both the locus coeruleus and the raphe nuclei project to the spinal cord where they gate sensory pathways from the skeletomuscular areas. As there is evidence that both noradrenaline and 5-HT are dysfunctional in depression, it is perhaps not surprising to find that the pain threshold is often reduced in patients with depression. Conversely, different types of antidepressants have been shown to have an antinociceptive effect in both rodent models of neuropathic pain, and clinically in fibromyalgia, chronic fatigue syndrome, postherpetic neuralgia and diabetic neuropathy. In general, it would appear that the dual action antidepressants (such as the TCAs and SNRIs) are more effective than the SSRIs. 

Capsaicin (Zostrix) is approved for the relief of pain following herpes zoster infection (postherpetic neuralgia). The drug depletes neurons of substance P, an endogenous neuropeptide that may mediate cutaneous pain. It is applied to affected skin after open lesions have healed. Local irritation is common. 

Unlabeled Uses Relief of neuropathic pain, such as that experienced by patients with diabetic neuropathy or postherpetic neuralgia treatment of anxiety, bulimia nervosa, migraine, nocturnal enuresis, panic disorder, peptic ulcer, phantom limb pain... 

Pregabalin is approved for the adjunctive treatment of partial seizures, with or without secondary generalization controlled clinical trials have documented its effectiveness. It is available only in oral form, and the daily dose ranges from 150 to 600 mg/d, usually in two or three divided administrations. Pregabalin is also approved for use in neuropathic pain, including painful diabetic peripheral neuropathy and postherpetic neuralgia. 

Over the years, antidepressant drugs have become an important treatment option in chronic pain states, in their own right and as adjuncts to opiate treatment. In fact, tricyclic antidepressants are the mainstay of treatment of neuropathic pain conditions such as polyneuropathy, diabetic neuropathy, postherpetic neuralgia and peripheral nerve injury (Sindrup, 1997 Sindrup and Jensen, 1999). Other chronic pain states responsive to antidepressants include osteo- and rheumatoid arthritis, fibromyalgia, and chronic tension headache. 

Rowbotham, M. C., Reisner-Keller, L. A., Fields, H. L. Both intravenous lidocaine and morphine reduce the pain of postherpetic neuralgia, Neurology 1991, 41, 1024-1028. 

Eisenberg, E., Kleiser, A., Dortort, A., Haim, T., Yarnitsky, D. The NMDA (N-methyl-D-aspartate) receptor antagonist memantine in the treatment of postherpetic neuralgia a double-blind, placebo-controlled study, Eur. J. Pain 1998, 2, 321-327. 

Pathological conditions in which capsaicin itself is not sufficiently active, but more potent vanilloids are expected to be of greater therapeutic value. For example diabetic neuropathy (Ross and Varipapa, 1989), postherpetic neuralgia (Watson et al., 1988 Bernstein et al., 1989), chronic distal painful polyneuropathy (Low et al., 1995), post-mastectomy pain syndrome (Watson et al., 1989), Guillain-Barre syndrome (Morgenlander et al., 1990), reflex sympathetic dystrophy (Cheshire and Snyder, 1990), vulvar vestibulitis (Friedrich, 1988). 

Capsaicin (Capsin, Zostrix, Others) [OTC] [Topical Anesthetic/ Analgesic] Uses Pain d/t postherpetic neuralgia, chronic neuralgia, arthritis, diabetic neuropathy, postop pain, psoriasis, intractable pruritus Action Topical analgesic Dose Apply tid-qid Caution [C, ] Disp Creams, gel, lotions, roll-ons SE Local irritation, neurotox, cough Interactions May T cough W/ ACEIs EMS ... 

Nelson K. A., Park K. M., Robinovitz E., Tsigos C., and Max M. B. (1997). High-dose oral dextromethorphan versus placebo in painful diabetic neuropathy and postherpetic neuralgia. Neurology 48 1212-1218. 

This pungent product is responsible for the intense irritant effects of topical Capsicum preparations. Repeated application of capsaicin can deplete and prevent reaccumulation of substance P, an endogenous mediator of pain impulses from the periphery to the CNS. Since the early 1990s, capsaicin cream has been available in the U.S. as an approved drug for relief of postherpetic neuralgia and pain due to diabetic neuropathy and osteoarthritis. 

Oral famciclovir is effective for the treatment of first and recurrent genital herpes attacks and for chronic daily suppression (Table 49-1). It is also used to treat acute herpes zoster (shingles). In controlled trials in immunocompetent patients with zoster, famciclovir was similar to acyclovir in rates of cutaneous healing but was associated with a shorter duration of postherpetic neuralgia. Comparison of famciclovir to valacyclovir for treatment of herpes zoster in immunocompetent patients showed similar rates of cutaneous healing and pain resolution. However, neither drug decreased the incidence of postherpetic neuralgia. 

Watson, C. P. N., and Babul, N. (1998). Efficacy of oxycodone in neuropathic pain A randomized trial in postherpetic neuralgia. Neurolog)) 50, 1837—1841. 

The local anesthetic lidocaine provides significant relief of neuropathic pain in the clinic when administered systemically at subanesthetic doses. In several placebo-controlled studies, intravenous infusions of lidocaine significantly reduced neuropathic pain at plasma concentrations of 1.5-5 pgmL 1 [59-61]. Lightheadedness is a common side effect at therapeutic doses, whereas cardiac depression is associated with plasma concentrations of 20-25 xgmL 1. A transdermal formulation of lidocaine is approved in the United States for the treatment of postherpetic neuralgia [62]. Orally available state-dependent Nayl blockers have shown efficacy in the clinic when appropriate plasma concentrations are achieved. 

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