Pain
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Comparative Study
Micromolar lidocaine selectively blocks propagating ectopic impulses at a distance from their site of origin.
Abnormal impulses caused by very slowly inactivating Na channels of peripheral nerve have been proposed to play a critical role in neuropathic pain. Low concentrations of local anesthetics, often effective in treating experimental and clinical neuropathic pain, are also known to potently suppress the long after-depolarizations induced by these persistently open Na channels. However, these drug actions on impulses that have propagated away from such sites are undetermined. ⋯ Tetrodotoxin also inhibited the induced spontaneous activity, but only at concentrations that also depressed the compound action potential spike. These findings show that low concentrations of lidocaine can restore normal firing patterns in nerve where hyperexcitability has been caused by delayed Na-channel inactivation, without acting directly at the site where ectopic impulses are generated. Thus, it appears that the pattern of abnormal activity rather than an abnormally gating Na channel per se can be a target for lidocaine's therapeutic action.
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Data on 40 upper limb amputees (11 bilateral) with regard to stump pain, phantom sensation and phantom pain is presented. All the patients lost their limbs as a result of violent injuries intended to terrorise the population and were assessed 10-48 months after the injury. All amputees reported stump pain in the month prior to interview and ten of the 11 bilateral amputees had bilateral pain. ⋯ In the bilateral amputees phantom sensation, phantom pain and telescoping all showed bilateral concordance, whereas stump pain and neuromas did not show concordance. About half the subjects (56%) had lost their limb at the time of injury (primary) while the remainder had an injury, then a subsequent amputation in hospital (secondary). There was no association between the incidence of phantom pain and amputation irrespective of being primary or secondary.
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A variety of molecules released by inflammatory reactions in the dorsal root and dorsal root ganglion (DRG) may play important roles in the pathology of neuronal abnormalities in lumbar disc herniation. In order to elucidate the pathophysiological mechanisms of painful radiculopathy, secondary to lumbar disc herniation, we evaluated pain-related behavior and the change of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) expression in the DRG and dorsal root using a rat model of lumbar disc herniation. In the nucleus pulposus (NP) group, the left L4/5 nerve roots were exposed after hemilaminectomies and autologous intervertebral discs, which were obtained from coccygeal intervertebral discs, were implanted on each of the exposed nerve roots without mechanical compression. ⋯ We also injected NGF into the endoneurial space of the normal rat spinal nerve root and found that the NGF injection produced dose-dependent mechanical allodynia on the ipsilateral hind paw at 1 day after surgery and an increase in the percentage of BDNF-IR neurons in the DRG at 3 days after surgery compared to the group receiving saline injection. These findings suggest that in the lumbar disc herniation model, i.e. neuritis of the nerve root, increased NGF produced by the inflammatory responses in the dorsal root and DRG tissues may affect the production of BDNF in the DRG and may play important roles in the modulation of the dorsal horn neurons. These changes in neurotrophic factors in the primary afferents may be involved in the pathophysiological mechanisms of neuropathic pain produced by lumbar disc herniation.
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Drugs that inhibit reuptake of monoamines are frequently used to treat pain syndromes, e.g. neuropathy or fibromyalgia, where mechanical allodynia is present. Several lines of evidence suggest the involvement of supraspinal sites of action of these drugs. However, a direct study of supraspinal serotonin (5-HT) or norepinephrine (NE) release in an animal model in which allodynia is expressed, e.g. neuropathy, has not been done. ⋯ This study is the first to demonstrate changes in monoamine release supraspinally in NP rats. The differential effect between VB thalamus and hypothalamus suggests that a terminal field change may be involved. Putative mechanisms for mediating this change include alterations of GABA-ergic systems and/or plasticity related to alterations in N-methyl-D-aspartate receptor activation and nitric oxide release related to afferent hyperactivity induced by neuropathic pain.
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Randomized Controlled Trial Clinical Trial
Anger and pain sensitivity in chronic low back pain patients and pain-free controls: the role of endogenous opioids.
The experience of anger (i.e. trait anger) and anger management style (i.e. anger-in, anger-out) are related to sensitivity to acute and chronic pain stimuli, although underlying mechanisms are unknown. This study tested whether anger variables are associated with impaired endogenous opioid antinociceptive activity, and whether these relationships differed between chronic pain patients and healthy normals. Forty-three chronic low back pain (LBP) sufferers and 45 pain-free normals received opioid blockade (8 mg naloxone i.v.) or placebo blockade (saline) in randomized, counterbalanced order in separate sessions. ⋯ Anger-out x LBP/normal interactions were non-significant, suggesting that links between anger-out and drug effects were similar for patients and normals. Controlling for depression did not eliminate the significant relationship between anger-out and drug effects. Findings suggest that anger-in and anger-out affect pain sensitivity through different mechanisms: only the effects of anger-out may be mediated by endogenous opioid dysfunction.