Articles: hyperalgesia.
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Activation of ERK (extracellular signal-regulated kinase) MAP (mitogen-activated protein) kinase in dorsal horn neurons of the spinal cord by peripheral noxious stimulation contributes to short-term pain hypersensitivity. We investigated ERK activation by peripheral inflammation and its involvement in regulating gene expression in the spinal cord and in contributing to inflammatory pain hypersensitivity. Injection of complete Freund's adjuvant (CFA) into a hindpaw produced a persistent inflammation and a sustained ERK activation in neurons in the superficial layers (laminae I-IIo) of the dorsal horn. ⋯ CFA-induced phospho-ERK primarily colocalized with prodynorphin and NK-1 in superficial dorsal horn neurons. Although intrathecal injection of U0126 did not affect basal pain sensitivity, it did attenuate both the establishment and maintenance of persistent inflammatory heat and mechanical hypersensitivity. Activation of the ERK pathway in a subset of nociceptive spinal neurons contributes, therefore, to persistent pain hypersensitivity, possibly via transcriptional regulation of genes, such as prodynorphin and NK-1.
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Neuropathic pain represents a series of relatively uncommon chronic pain conditions, caused by lesions or dysfunctions of peripheral or central afferent pathways in the nervous system. The symptoms and signs of neuropathic pain can all be explained by a neuronal hyperexcitability at the site of the nerve lesion, which subsequently and in a dynamic fashion recruits more central sites. The manifestations of such neuronal hyperexcitability are therefore rather similar, irrespective of the causes or sites of the lesions. ⋯ Our understanding of the mechanisms underlying neuronal hyperexcitability has increased dramatically within the last decade, and accordingly, it has been suggested that pain be classified according to a mechanism-based approach. The challenge for an improved understanding of neuropathic pain--which is the key for better treatment--lies in elucidating the relationships between symptoms, signs, aetiology, anatomical lesions, and underlying mechanisms. At present, this is not a trivial task.
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Randomized Controlled Trial Clinical Trial
Concentration-effect relationships for intravenous alfentanil and ketamine infusions in human volunteers: effects on acute thresholds and capsaicin-evoked hyperpathia.
The authors have extended preclinical studies on pain to human volunteers by examining the effects of intravenous alfentanil and ketamine on acute sensory thresholds andfacilitated processing induced by intradermal capsaicin. Eleven healthy subjects received targeted plasma concentrations of alfentanil, ketamine, and placebo followed by neurosensory testing (thermal and von Frey hair thresholds). After completing the tests at the highest plasma level, intradermal capsaicin was injected into the volar aspect of the left forearm, and the flare response and hyperalgesia to von Frey hair, stroking, and heat were assessed. ⋯ Ketamine significantly decreased capsaicin-induced von Frey hair hyperalgesia. Both drugs resulted in a significant elevation of von Frey hair-induced pain thresholds and a decrease in capsaicin-induced pain. These studies suggest that experimental human pain models may be used to study analgesic pharmacology and may serve as important methods for defining the analgesic efficacy of drugs in phase I clinical trials.
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While it may be convenient to categorize neuropathic pain syndromes on the basis of anatomical distribution or disease state (e.g., diabetic neuropathy, radiculopathy, postherpetic neuralgia), the treatment of neuropathic pain, alone, should also consider the signs and symptoms and the underlying putative mechanisms that may then be inferred from each individual's signs and symptoms. A diagnosis-based approach to treatment may not effectively relieve a patient's pain or improve his or her quality of life, the ultimate goal of treatment. Although research that supports a symptom- and mechanism-based approach to treating neuropathic pain is ongoing and dynamic, the preclinical and clinical data available thus far form an initial rational framework within which we may attempt to target putative pain mechanisms.
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The aim of the present study was to investigate the effect of the rate of temperature increase on the intensity of the evoked pain before and after hyperalgesia induced by topical capsaicin. Further, hyperalgesia to suprathreshold heat stimuli was investigated. Thirteen healthy volunteers were included in the experiment. ⋯ Increased ratings were found for all three heating rates in the secondary hyperalgesic area. There were no heat hyperalgesia in the control arm. In conclusion, hyperalgesia to suprathreshold heat stimuli was observed in the secondary hyperalgesic area and C-fibres play an important role in the primary hyperalgesia to heat.