Pain | May 23, 2014 | Author: The Super Pharmacist
Neuropathic pain is a type of chronic pain that occurs when nerves become injured or damaged. These damaged nerve fibers send incorrect pain signals to the brain. Neuropathic pain is characterised by spontaneous pain (ongoing and/or paroxysmal) and evoked pain in response to certain stimuli.1 In its latest 2011 update, the International Association for the Study of Pain (IASP) and its Special Interest Group on Neuropathic Pain (neuPSIG) defines neuropathic pain as "pain caused by a lesion or disease of the somatosensory nervous system."2 The somatosensory system is the part of the sensory system concerned with the conscious perception of touch, pressure, pain, temperature, position, movement, and vibration, which arise from the muscles, joints, skin, and fascia.3 Many common diseases, such as diabetic neuropathy, postherpetic neuralgia, trigeminal neuralgia, spinal cord injury, cancer, stroke, and multiple sclerosis can cause neuropathic pain. A characteristic feature of neuropathic pain is the coexistence of negative and positive symptoms and signs, reflecting loss-of-function and gain-of-function of the somatosensory system, respectively.4 Patients with neuropathic pain usually show both negative and positive symptoms and signs.Representativenegative symptoms include loss of sensation, muscle atrophy and weakness. Examples of positive symptoms are paresthesias and dysesthesias. Paresthesias are spontaneous abnormal sensations such as numbness and tingling which can be annoying. Dysesthesias are more severe unpleasant sensations provoked in response to relatively innocuous stimuli such as light touch, mild heat or cold. This type of abnormal pain response which is disproportionate to the inciting stimulus (pain in response to a normally nonpainful stimulus) is termed "allodynia."
As many as one in 20 Australians suffers from fibromyalgia,5 a condition that causes chronic widespread pain and which is commonly accompanied by fatigue, sleep disturbance, cognitive difficulties, anxiety and/or depression, and impairment of daily function. "Chronic" indicates that the pain and tenderness have been present continuously for at least 3 months. "Widespread" means that the pain and tenderness are on both sides of the body, above and below the waist, including the axial spine.6 Fibromyalgia is currently understood to be a disorder of central pain processing or a syndrome of central sensitivity rather than dysfunction in the peripheral tissues where pain is perceived.6, 7 It has been described as a diffuse problem of sensory “volume control” such that patients have a lower threshold of pain and of other stimuli, such as heat, noise, and strong odors.8
Fibromyalgia is not universally recognised as a neuropathic pain syndrome. Some members of the scientific community reject this hypothesis vehemently. However, many authorities have become convinced that it does represent a neuropathic pain state.9, 10, 11 They point out thatneuropathic pain is stimuli-independent and is accompanied by allodynia and paresthesia, both of which are also common features of fibromyalgia. Evidence indicates that, in fact, most fibromyalgia patients have paresthesias.12However, a specific nerve lesion has not been identified in patients with fibromyalgia, or has it? Several recent studies have demonstrated the presence of small fiber neuropathy in a significant number of fibromyalgia patients thus supporting the idea that fibromyalgia may, in fact, be a neuropathic pain syndrome.13, 14
The treatment of chronic pain in fibromyalgia should combine non-pharmacologic with pharmacologic management. A stepwise program of gradual but regular exercise has been shown to provide the most benefit. Patients must learn how to pace themselves by balancing periods of activity and rest. Relaxation techniques including meditation, yoga, visual imagery and breath work can help to manage stress. Many studies have found elevated rates of trauma, victimisation, and interpersonal conflict among people with fibromyalgia.15Post-traumatic stress disorder has also been linked to fibromyalgia.16Cognitive behavioral therapy is recommended to address these issues. The goals of these interventions are to reduce both physical and psychological distress and promote self-efficacy and self-management in patients with fibromyalgia. Poor sleep worsens and perpetuates fibromyalgia symptoms mandating treatment.6 Patients should be educated on the proper sleep hygiene (e.g. avoiding caffeinated drinks or a large evening meal before bedtime). If this fails to improve sleep, medications may be indicated. Acupuncture, chiropractic manipulation, and myofascial release can be beneficial in fibromyalgia, but results may be short-lived, and patients may not be able to afford these types of long-term therapy.
Analgesics Analgesics such as acetaminophen (Panadol) and non-steroidal antiinflammatory drugs such as ibuprofen (Advil, Nurofen) are of limited efficacy in reducing pain due to fibromyalgia. No solid evidence has shown that narcotics are effective for the chronic pain of fibromyalgia and continued use presents a risk of physical or psychological dependence.17 Tramadol is a centrally acting analgesic indicated for moderately severe pain and may prove beneficial in fibromyalgia. Tramadol also inhibits reuptake of norepinephrine and serotonin.
Antidepressants These drugs help elevate levels of serotonin and norepinephrine in the central nervous system. Low levels of these chemicals are associated with depression, pain and fatigue.
Tricyclic antidepressants (TCAs) The mechanism by which TCAs improve symptoms of fibromyalgia is not fully understood. TCAs inhibit the reuptake of serotonin and norepinephrine in spinal neurons, thus increasing their synaptic concentrations. This is thought to result in analgesic effects through the neurotransmitters' action on the descending pain pathways.18TCAs act on pain at dosages much lower (25 mg daily for amitriptyline hydrochloride) than are needed for effective treatment of depression (100–150 mg daily). TCAs have short-term efficacy in treating pain, improving sleep and improving the sense of well-being in patients with fibromyalgia. However, adverse effects (eg, dry mouth, drowsiness, weight gain) limit patient tolerance for long-term use.19
Selective serotonin reuptake inhibitors (SSRIs) SSRIs which include fluoxetine (Prozac), citalopram (Celepram), escitalopram (Lexapro), fluvoxamine, paroxetine (Aropax), and sertraline (Zoloft) improve symptoms in fibromyalgia but have largely been replaced as treatment for pain by dual serotonin/norepinephrine reuptake inhibitors (SNRIs). In general, SSRIs are better tolerated than TCAs because they have fewer anticholinergic adverse effects; however, they have been found to be less effective than TCAs for the treatment of the pain of fibromyalgia.20
Serotonin/norepinephrine reuptake inhibitors (SNRIs) SNRIs such as venlafaxine (Effexor), desvenlafaxine (Pristiq), milnacipram,21 or duloxetine (Cymbalta)22, 23, 24 have been shown to be significantly superior to placebo in providing pain relief, reducing fatigue and improving physical and mental performance. Safety studies indicate that duloxetine is safe and well tolerated. Duloxetine (Cymbalta) and milnacipram are FDA approved for the treatment of fibromyalgia. The Australian Drug Regulation Agency, the Therapeutic Goods Administration (TGA), has granted the French drug company Pierre Fabre Medicament marketing authorisation for Joncia, the brand name for the drug Milnacipran in the treatment of fibromyalgia. This approval occurred on the 17th November 2011 and is the first time any drug has been approved for treatment of fibromyalgia in Australia.
Anticonvulsants These agents are useful for chronic pain states, including fibromyalgia, and are useful adjunctive medications for disturbed sleep and depression. These include gabapentin (Neurontin),26 and the more recently released pregabalin (Lyrica).27, 28, 29 Pregabelin (Lyrica) is FDA approved for the treatment of fibromyalgia. Pregabalin (Lyrica) has recently been approved for the treatment of neuropathic pain on the Pharmaceutical Benefits Scheme (PBS) in Australia. The PBS provides subsidised prescription drugs to residents of Australia.
Nonbenzodiazepine hypnotics Zolpidem (Stilnox) is indicated for insomnia.31 It is structurally dissimilar to benzodiazepines but similar in activity, with the exception of having reduced effects on skeletal muscle and seizure threshold.
Muscle relaxants With the exception of cyclobenzaprine, long-term improvement over placebo has not been established for muscle relaxants in fibromyalgia, and they are not recommended. Cyclobenzaprine, however, has been demonstrated to be helpful for sleep and pain control as a single nighttime dose in combination with an anxiolytic/hypnotic agent.31 This agent is structurally related to tricyclic antidepressants (TCAs).
Dopamine agonists Several studies have investigated the utility of dopamine agonists in the treatment of fibromyalgia. The best known of these is the report of a controlled trial of the dopamine agonist pramipexole. Compared with the placebo group, patients receiving pramipexole experienced significant improvement in measures of pain as reflected by an average 36% decrease in the visual analog pain scale across the active treatment group, with 42% of these achieving >50% decrease in pain (as compared to 17% of those on placebo). A number of other measures, such as fatigue and global well-being, likewise showed significant symptom improvement.31
As compared to placebo, duloxetine, tramadol, milnacipran, and gabapentin, pregabalin has been shown to be the most cost-effective treatment for patients with severe fibromyalgia.32