Articles: hyperalgesia.
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The pathogenesis of pain in chronic pancreatitis (CP) is poorly understood and treatment remains difficult. We hypothesized that nerve growth factor (NGF) plays a key role in this process via its effects on the transient receptor potential vanilloid 1, TRPV1. ⋯ These findings emphasize a key role for NGF in pancreatic pain and highlight the role it plays in the modulation of TRPV1 expression and activity in CP.
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Neurogastroenterol. Motil. · Jul 2011
Role of neuronal nitric oxide synthase in colonic distension-induced hyperalgesia in distal colon of neonatal maternal separated male rats.
Nitric oxide (NO) is implicated in the pathogenesis of irritable bowel syndrome (IBS) but the underlying mechanism is unclear. Thus, the aim of the present study is to examine the role of NO synthase (NOS) expression in the distal colon of neonatal maternal separation (NMS) model rats employed in IBS studies. ⋯ Neonatal maternal separation increased the NO generation by nNOS upregulation that interact with reactive oxygen species contributing to the visceral hypersensitivity in IBS.
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Chronic widespread pain, such as observed in irritable bowel (IBS) and fibromyalgia (FMS) syndrome, are markedly affected by stress. While such forms of stress-induced hyperalgesia are generally considered manifestations of "central sensitization," recent studies in patients with IBS and FMS suggest an additional, peripheral contribution. ⋯ Stress also induced an increase in conduction velocity from 1.25 m/s to 2.09 m/s, and increased variability in neuronal activity. Given that these changes, each of at least moderate magnitude, would be expected to enhance nociceptor activity, it is likely that, taken together, they contribute to the enhanced nociception observed in this model of stress-induced chronic widespread pain.
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Neuropathic pain is currently being treated by a range of therapeutic interventions that above all act to lower neuronal activity in the somatosensory system (e.g. using local anesthetics, calcium channel blockers, and opioids). The present review highlights novel and often still largely experimental treatment approaches based on insights into pathological mechanisms, which impact on the spinal nociceptive network, thereby opening the 'gate' to higher brain centers involved in the perception of pain. Cellular and molecular mechanisms such as ectopia, sensitization of nociceptors, phenotypic switching, structural plasticity, disinhibition, and neuroinflammation are discussed in relation to their involvement in pain hypersensitivity following either peripheral neuropathies or spinal cord injury. ⋯ Subsequently, identification of the therapeutic window-of-opportunities for each specific intervention in the particular peripheral and/or central neuropathy is essential for successful clinical trials. Most of the cellular and molecular pain mechanisms described in the present review suggest pharmacological interference for neuropathic pain management. However, also more invasive treatment approaches belong to current and/or future options such as neuromodulatory interventions (including spinal cord stimulation) and cell or gene therapies, respectively.
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It has been reported that intracerebroventricular injection of a μ receptor antagonist blocked 2 but not 100Hz electroacupuncture (EA)-produced analgesia in an uninjured animal model. Because persistent pain changes neural response to external stimulation, we hypothesized that the mechanisms of EA anti-hyperalgesia may be different in persistent pain than in health. Hyperalgesia, decreased paw withdrawal latency (PWL) to a noxious thermal stimulus, was induced by subcutaneously injecting complete Freund's adjuvant (CFA) into the hind paws of rats. ⋯ In summary, EA may induce release of endogenous endomorphins that activate μ opioid receptors in GABAnergic neurons to suppress the release of GABA. This removes the tonic inhibition of GABA on serotonergic neurons in the RVM, and activation of these serotonergic neurons inhibits pain. EA may be used as complementary treatment for inflammatory pain.