Articles: hyperalgesia.
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Anesthesia and analgesia · Jan 2004
Amiodarone decreases heat, cold, and mechanical hyperalgesia in a rat model of neuropathic pain.
Lidocaine is effective in controlling ventricular dysrhythmia and neuropathic pain. Amiodarone, like lidocaine, has sodium channel blocking properties. In the present study we explore whether amiodarone has a similar effect as lidocaine on the heat, cold, and mechanical hyperalgesia seen in the rat model of neuropathic pain. Ten male Sprague-Dawley rats were anesthetized. Four loose ligatures were placed on the sciatic nerve of the right hindpaw. A sham operation was performed on the contralateral hindpaw (control). Heat hyperalgesia was determined by comparing each paw withdrawal latency to heat stimulation (radiant heat source, 50 degrees C). Cold hyperalgesia was assessed with acetone application. Mechanical hyperalgesia was determined by comparing the mechanical threshold in the ligated and control hind paws using calibrated von Frey filaments. Amiodarone was intraperitoneally administered at doses of 1, 5, 10, 20, 50, and 100 mg/kg after the development of hyperalgesia. The animals were tested for hyperalgesia before and 1, 3, and 24 h after the administration of a single dose of amiodarone. Intrathecal catheters were implanted in 5 new rats, and amiodarone 5 mg/kg was injected. Testing for heat, mechanical, and cold hyperalgesia was performed similarly in the intrathecal amiodarone administration group. Amiodarone produces statistically significant decreases of heat, cold, and mechanical hyperalgesia after intraperitoneal administration. Results are statistically significant at 10 mg/kg (heat hyperalgesia), 20 mg/kg (mechanical hyperalgesia), and 100 mg/kg (cold hyperalgesia) intraperitoneally. Hyperalgesia returns 24 h after a dose. The intrathecal administration of amiodarone produces a nonstatistically significant reduction of hyperalgesia. Amiodarone seems to have a similar effect as lidocaine on the hyperalgesia seen in the rat model of neuropathic pain. As the half-life of amiodarone is significantly longer that that of lidocaine (mean, 53 days versus 90 min) in humans, it may have the potential to provide a longer lasting (and perhaps more effective) effect than lidocaine on neuropathic pain states. ⋯ Amiodarone was found to produce a statistically significant decrease in heat, cold, and mechanical hyperalgesia in a rat model of neuropathic pain after intraperitoneal injection. Considering its long half-life in humans, amiodarone has the potential to provide long lasting pain relief in neuropathic pain states.
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J Pain Palliat Care Pharmacother · Jan 2004
ReviewOpioid insights:opioid-induced hyperalgesia and opioid rotation.
Opioid analgesics are an irreplaceable component of pharmacotherapy of numerous pain-producing conditions. Clinicians and patients must contend with the imperfect nature of this class of drugs, trying to balance benefits and burdens on a continual basis. New literature related to evidence-based selection of opioids and the neurobiological phenomenon of opioid induced hyperalgesia are reviewed. A matrix describing critical elements in the selection of opioid analgesics, both for initial therapy and for opioid rotation, is presented.
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Cutaneous allodynia, pain resulting from application of a non-noxious stimulus to normal skin, is a recently described symptom of migraine, with a potential role in directing optimal treatment for migraine attacks. Manifestations of cutaneous allodynia include discomfort when combing the hair, shaving, and wearing glasses, contact lenses, earrings or tight clothing. The exact mechanism by which a migraine attack is triggered is not known, but it has been theorised that, in some patients, once the attack has begun, central neurons can propagate information about the pain process without the need for further external stimuli. ⋯ The serotonin 5-HT(1B/1D) agonist anti-migraine agents (the 'triptans') block meningeal nociceptor transmission at presynaptic sites in the dorsal horn. Studies have shown that triptan therapy can abort pain prior to the development of central sensitisation, but not after allodynia has been established. Therefore, in the subset of patients who report symptoms of cutaneous allodynia with migraine attacks, early initiation of triptan therapy is currently the best intervention to achieve rapid, complete and sustained pain relief.
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Physiological and pharmacological evidence both have demonstrated a critical role for voltage-gated sodium channels (VGSCs) in many types of chronic pain syndromes because these channels play a fundamental role in the excitability of neurons in the central and peripheral nervous systems. Alterations in function of these channels appear to be intimately linked to hyperexcitability of neurons. ⋯ This review focuses on the role of VGSCs in the hyperexcitability of sensory primary afferent neurons and their contribution to the inflammatory or neuropathic pain states. The discrete localization of the tetrodotoxin (TTX)-resistant channels, in particular NaV1.8, in the peripheral nerves may provide a novel opportunity for the development of a drug targeted at these channels to achieve efficacious pain relief with an acceptable safety profile.
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Prostaglandin E2 (PGE2) produced in the medial preoptic region (MPO) in response to immune signals is generally accepted to play a major role in triggering the illness response, a complex of physiological and behavioral changes induced by infection or injury. Hyperalgesia is now thought to be an important component of the illness response, yet the specific mechanisms through which the MPO acts to facilitate nociception have not been established. However, the MPO does project to the rostral ventromedial medulla (RVM), a region with a well-documented role in pain modulation, both directly and indirectly via the periaqueductal gray. ⋯ In animals displaying behavioral hyperalgesia, the PGE2 microinjection activated on-cells, RVM neurons thought to facilitate nociception, and suppressed the firing of off-cells, RVM neurons believed to have an inhibitory effect on nociception. A large body of evidence has implicated prostaglandins in the MPO in generation of the illness response, especially fever. The present study indicates that the MPO also contributes to the hyperalgesic component of the illness response, most likely by recruiting the nociceptive modulating circuitry of the RVM.