Neuropathic/Chronic Pain Treatments

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. 

Cono toxins represent one of the more inspiring examples of marine toxins because of their outstanding biological activities in their habitat, in the sea, as well as their being drug leads.Ziconotide, (Prialt) a 25 amino acid peptide isolated from cones, became the first FDA approved drug for the treatment of neuropathic pain and severe chronic pain that do not respond to other forms of treatment. 

Opioids are used for the treatment of moderate to severe or very severe pain of acute or chronic type (Stein, 1999). Nearly all forms of pain are sensitive to opioid treatment and in contrast to traditional opinions even neuropathic pain is reasonably sensitive to higher doses of opioids. This was clearly shown in well-controlled clinical studies (Watson, 2000). The most important use of opioids in acute pain treatment is postoperative pain, whereas treatment of cancer pain, often accompanied by a neuropathic pain component, is the classical domain of chronic opioid treatment. 

Analgesic efficacy and clinical use Morphine (Benyhe, 1994) is a very potent analgesic and is used for the treatment of moderate to severe acute and chronic pain of various origins. It is more active in nociceptive and in inflammatory as compared to neuropathic pain and is regarded as the gold standard for pain treatment (Coluzzi,1998). 

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. 

In contrast to its non-significant effects when administered i.t. in the formalin-test, i.t. treatment with (S)-4CPG was effective at significantly reducing neuropathic-like pain behavior in nerve-injured rats (Fisher et al., 1998 Yashpal et al., 2001 for a review see Fundytus, 2001). Consistent with the behavioural effects, there is evidence that chronic constriction injury induced increases in the translocation and activation of spinal PKC dependent on activity at mGlu1/5 receptors (Yashpal et al., 2001). 

Amitriptyline is usually the treatment of choice for neuropathic pain. Some selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine (Prozac ),paroxetine (Paxil ),sertraline (Zoloft ), and clomipramine (Anafranil ) can be used, but they don t appear to be as effective as TCAs. The doses for TCAs in treating neuropathic pain are usually lower than those for treating depression, and the drugs usually start to take effect more quickly in relieving pain than they do in relieving depression. It is interesting that people who suffer from chronic pain often experience symptoms of depression, so TCAs can benefit these people by helping to ease not only their pain but also their depressed mood. 

Local application of concentrated sodium channel blockers can provide complete pain relief through nerve conduction block (local anesthetics). This approach to pain relief is limited to a few applications involving short-term treatment of acute pain, since sodium channels are also vital to conduction in the heart, CNS, skeletal muscle, and non-nociceptive sensory neurons. However, some types of chronic pain signaling appear to be sensitive to sodium channel blockers at concentrations that do not cause conduction block. In particular, neuropathic pain, defined as chronic pain resulting from a primary lesion or dysfunction of the peripheral nervous system by the International Association for the Study of Pain (IASP) [58], is thought to originate from aberrant signaling in the nervous system and can be ameliorated by sodium channel blockers. 

The goal ot treatment ot chronic pain conditions such as neuropathic pain, fibromyalgia, headaches, low back pain, and neck pain Is to reduce symptoms as much as possible, especially In combination with other treatments... 

Tricyclic antidepressants are used to treat depression. They are also used for treatment of enuresis in children, chronic pain syndromes, neuropathic pain, the fibromyalgia syndrome, and chronic headaches. 

Chronic pain patients tend to have concurrent depression however, the antidepressants chosen may not have any pain-relieving properties. Antidepressants that affect one neurotransmitter in the brain, such as selective serotonin reuptake inhibitors have not appeared to be effective in the management of pain in clinical trials. Antidepressants that affect multiple neurotransmitters— namely, serotonin and norepinephrine—have been shown to be effective pain relievers.Two published metaanalyses have shown that tricyclic antidepressants amitriptyline, desipramine, imipramine, and nortriptyline are the most effective treatment for the management of neuropathic pain. ° These publications review the published clinical trial data for all agents available for the management of neuropathic pain. 

Pharmacists in ambulatory settings may work in chronic pain clinics as part of the treatment team. These clinicians perform extensive medication reviews and provide alternatives when treatments fail. Pharmacists who work with diabetic patients may be responsible for managing neuropathic pain. 

Taken together, these results show that the endocannabinoid system plays an important role in the physiological modulation of nociceptive transmission and in the development of inflammatory and neuropathic pain. Furthermore, the endocannabinoid system seems to participate in the antinociception induced by anti-inflammatory drugs, and displays an important synergic effect with opioid agonists. These data strongly support the therapeutic potential of cannabinoid receptor agonists for the treatment of chronic pain. 

Several psychosomatic disorders may respond at least partly to treatment with tricyclic antidepressants, MAO inhibitors, or SSRIs among these are chronic pain disorders, including diabetic and other peripheral neuropathic syndromes (for which tertiary-amine tricyclics probably are... 

Spinal cavernomas are a specific problem. The vast majority ( 80%) of patients who initially present with neuropathic pain due to spinal cavernoma hemorrhage may suffer a chronic pain syndrome after resection of the lesion. The experience of Cohen-Gadol et al. (2006) is that neuropathic pain due to cavernoma hemorrhage is refractory to surgical treatment. Therefore, the pain associated with spinal cavernoma hemorrhage may not provide adequate justification for surgical therapy. Prophylactic surgery in spinal cavernoma is not recommended. 

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