Articles: hyperalgesia.
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In this paper, the relationships between neural mechanisms of persistent pain and the neural representations of these conditions in the human and animal brain will be reviewed. Animal models of chronic pain, such as the sciatic nerve constrictive injuries, are accompanied by somatotopically organized increases in several pain-related areas of the brain. ⋯ This suggests that these somatic and visceral hyperalgesic states may be represented by increased activity in the same cerebral pathways and centers that are involved in nociceptive stimuli in normal individuals. Hyperalgesic states during clinically relevant pain are especially reflected in brain areas such as the anterior cingulate and prefrontal cortical regions.
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Extracellular signal-regulated protein kinase (ERK) is a mitogen-activated protein kinase (MAPK) that mediates intracellular signal transduction in response to a variety of stimuli. ERK is involved in cell proliferation and differentiation and in neuronal plasticity, including long-term potentiation, learning, and memory. Here, we present recently accumulating data about the roles of MAPK pathways in mediating the neuronal plasticity that contributes to pain hypersensitivity. ⋯ On the other hand, peripheral inflammation and axotomy also induces p38 MAPK activation in DRG neurons. Taken together, these findings indicate that activation of MAPK in nociceptive neurons may participate in generating pain hypersensitivity through transcription-dependent and -independent means. Thus, inhibition of MAPK signaling in the primary afferents, as well as in the spinal cord, may provide a fruitful strategy for the development of novel analgesics.
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Review
Neuroimmune activation and neuroinflammation in chronic pain and opioid tolerance/hyperalgesia.
One area that has emerged as a promising therapeutic target for the treatment and prevention of chronic pain and opioid tolerance/hyperalgesia is the modulation of the central nervous system (CNS) immunological response that ensues following injury or opioid administration. Broadly defined, central neuroimmune activation involves the activation of cells that interface with the peripheral nervous system and blood. ⋯ CNS innate immunity and Toll-like receptors, in particular, may be vital players in this orchestrated immune response and may hold the answers to what initiates this complex cascade. The challenge remains in the careful perturbation of injury/opioid-induced neuroimmune activation to down-regulate this process without inhibiting beneficial CNS autoimmunity that subserves neuronal protection following injury.
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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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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.