Pain
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Comparative Study
Peripheral axonal injury results in reduced mu opioid receptor pre- and post-synaptic action in the spinal cord.
In both the spared nerve injury (SNI) and spinal nerve ligation (SNL) rat peripheral neuropathic pain models the presynaptic inhibitory effect of the mu opioid receptor (MOR) agonist (DAMGO) on primary afferent-evoked excitatory postsynaptic currents (EPSCs) and miniature EPSCs in superficial dorsal horn neurons is substantially reduced, but only in those spinal cord segments innervated by injured primary afferents. The two nerve injury models also reduce the postsynaptic potassium channel opening action of DAMGO on lamina II spinal cord neurons, but again only in segments receiving injured afferent input. The inhibitory action of DAMGO on ERK (extracellular signal-regulated kinase) activation in dorsal horn neurons is also reduced in affected segments following nerve injury. ⋯ Decreased activation of MOR on injured primary afferent central terminals and the second order neurons they innervate may minimize any reduction by opioids of the spontaneous pain mediated by ectopic input from axotomized small diameter afferents. Retention of MOR expression and activity in nearby non-injured afferents will enable, however, an opioid-mediated reduction of stimulus-evoked and spontaneous pain carried by intact nociceptor afferents and we find that intrathecal DAMGO (1000 ng) reduces mechanical hypersensitivity in rats with SNL. Axotomy-induced changes in MOR may contribute to opioid- insensitive components of neuropathic pain while the absence of these changes in intact afferents may contribute to the opioid sensitive components.
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Comparative Study Clinical Trial
The impact of ethnic differences in response to capsaicin-induced trigeminal sensitization.
Ethnic differences in the experience of pain, pain-related health care utilization and pain-reducing activities have been reported. Thus, evaluating of such variations is important in clinical and experimental pain. Since clinical pain is greatly influenced by disease-specific factors (severity, duration, type and treatment), evaluating ethnic differences in experimental pain models may not only provide some information about underlying mechanisms but also may predict or explain group differences in clinical pain. ⋯ Pain sensitivity, secondary hyperalgesic area, and pressure pain threshold were assessed. Overall, the model showed significant greater pain responses in South Indians (8.75+/-1.25 cm pain intensity and 9.33+/-2.32 cm2 hyperalgesic area) compared to Caucasians (6.25+/-1.95 cm pain intensity and 6.25+/-1.41 cm2 hyperalgesic area). The model may provide important information for further clinical research, e.g. migraine or differences in mechanisms underlying trigeminal sensitization.
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Comparative Study
Psychometric properties of the TSK-11: a shortened version of the Tampa Scale for Kinesiophobia.
The Tampa Scale for Kinesiophobia (TSK) is one of the most frequently employed measures for assessing pain-related fear in back pain patients. Despite its widespread use, there is relatively little data to support the psychometric properties of the English version of this scale. This study investigated the psychometric properties of the English version of the TSK in a sample of chronic low back pain patients. ⋯ In respect of specific cut-off scores, a reduction of at least four points on both measures maximised the likelihood of correctly identifying an important reduction in fear of movement. Overall, the TSK-11 possessed similar psychometric properties to the original TSK and offered the advantage of brevity. Further research is warranted to investigate the utility of the new instrument and the cut-off scores in a wider group of chronic pain patients in different clinical settings.
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Comparative Study
Mechanisms involved in the nociception produced by peripheral protein kinase c activation in mice.
Protein kinase C (PKC) is able to phosphorylate several cellular components that serve as key regulatory components in signal transduction pathways of nociceptor excitation and sensitisation. Therefore, the present study attempted to assess some of the mechanisms involved in the overt nociception elicited by peripheral administration of the PKC activator, phorbol 12-myristate 13-acetate (PMA), in mice. The intraplantar (i.pl.) injection of PMA (16-1600 pmol/paw), but not its inactive analogue alpha-PMA, produced a long-lasting overt nociception (up to 45 min), as well as the activation of PKCalpha and PKCepsilon isoforms in treated paws. ⋯ Finally, mast cells as well as capsaicin-sensitive and sympathetic fibres, but not neutrophil influx, mediated the nociceptive effect produced by PMA. Collectively, the results of the present study have shown that PMA injection into the mouse paw results in PKC activation as well as a relatively delayed, but long-lasting, overt nociceptive behaviour in mice. Moreover, these results demonstrate that PKC activation exerts a critical role in modulating the excitability of sensory neurons.
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Questions have been raised about the potential neurotoxicity of the neuraxial use of ketamine although ketamine and its active enantiomer S(+)-ketamine have been used intrathecally and epidurally (caudally) for the management of perioperative pain and in a variety of chronic pain syndromes. Clinical experience following neuraxial administration of S(+)-ketamine has been documented without reference to local central nervous system toxicity following this approach. ⋯ However, postmortem observation of the spinal cord and nerve roots revealed severe histological abnormalities including central chromatolysis, nerve cell shrinkage, neuronophagia, microglial upregulation, and gliosis. Based on our results, neuraxial administration of S (+)-ketamine cannot be recommended for clinical practise before a systematic study of toxicology of neuraxial S(+)-ketamine in animals or humans has been performed.