Pain
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Previous findings indicate that the brain stem descending system becomes more active in modulating spinal nociceptive processes during the development of persistent pain. The present study further identified the supraspinal sites that mediate enhanced descending modulation of behavior hyperalgesia and dorsal horn hyperexcitability (as measured by Fos-like immunoreactivity) produced by subcutaneous complete Freund's adjuvant (CFA). Selective chemical lesions were produced in the nucleus raphe magnus (NRM), the nuclei reticularis gigantocellularis (NGC), or the locus coeruleus/subcoeruleus (LC/SC). ⋯ The persistent hyperalgesia and neuronal hyperexcitability may be mediated in part by a descending pain facilitatory system involving NGC. Thus, the intensity of perceived pain and hyperalgesia is fine-tuned by descending pathways. The imbalance of these modulating systems may be one mechanism underlying variability in acute and chronic pain conditions.
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Safe and efficient use of spinal drugs requires neurotoxicologic animal studies before ethical application. We have evaluated the neurotoxicologic interruptions of intrathecal administration of midazolam in rabbits. Eighteen white New Zealand rabbits were randomly assigned into three groups consisting of six rabbits each. ⋯ Light and fluorescence microscopy evaluations were performed on transverse spinal cord sections by a neurohistopathologist in a blind fashion. Midazolam and preservative free midazolam treated rabbits showed significant histologic changes in light and fluorescence microscopy. The histologic and vascular lesions with the use of midazolam and preservative free midazolam suggested neurotoxic effects; thus chronic intrathecal administration of midazolam should be avoided in humans.
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Clinical Trial Controlled Clinical Trial
Nefopam strongly depresses the nociceptive flexion (R(III)) reflex in humans.
Nefopam hydrochloride has been commercialized as an analgesic drug in most Western European countries for 20 years. It has been shown to possess analgesic activity with a profile distinct from that of opioids or anti-inflammatory drugs. In order to define the mechanisms of action of this pharmacological agent, we studied, in a double-blind and cross-over fashion, its effects on the nociceptive flexion (R(III)) reflex and the corresponding pain sensation in ten healthy volunteers. ⋯ However, complementary peripheral mechanisms cannot be excluded on the basis of the present study. In view of these results, it seems that new clinical studies will have to be undertaken to revisit this potent analgesic agent and try to limit its adverse effects (i.e. nausea, vomiting, sweating). Its fast onset of action could clearly be an advantage, notably in the treatment of post-operative pain.
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Clinical Trial
Pain-related fear is more disabling than pain itself: evidence on the role of pain-related fear in chronic back pain disability.
There is growing evidence for the idea that in back pain patients, pain-related fear (fear of pain/physical activity/(re)injury) may be more disabling than pain itself. A number of questionnaires have been developed to quantify pain-related fears, including the Fear-Avoidance Beliefs Questionnaire (FABQ), the Tampa Scale for Kinesiophobia (TSK), and the Pain Anxiety Symptoms Scale (PASS). A total of 104 patients, presenting to a rehabilitation center or a comprehensive pain clinic with chronic low back pain were studied in three independent studies aimed at (1) replicating that pain-related fear is more disabling than pain itself (2) investigating the association between pain-related fear and poor behavioral performance and (3) investigating whether pain-related fear measures are better predictors of disability and behavioral performance than measures of general negative affect or general negative pain beliefs (e.g. pain catastrophizing). ⋯ Even when controlling for sociodemographics, multiple regression analyses revealed that the subscales of the FABQ and the TSK were superior in predicting self-reported disability and poor behavioral performance. The PASS appeared more strongly associated with pain catastrophizing and negative affect, and was less predictive of pain disability and behavioral performance. Implications for chronic back pain assessment, prevention and treatment are discussed.
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The behaviour of rats with spinal nerve ligation-induced neuropathic pain was studied using tests developed to measure depression and anxiety. Adult male Sprague-Dawley rats were tested with the open field test, elevated plus maze, two compartment test and forced swimming test. Spontaneous motility was measured in a photocell observation box. ⋯ The results were also comparable when rats that developed a high degree of neuropathy were compared with the rats with low degree of neuropathy and the sham operated group. In conclusion, spinal nerve ligation injury of the spinal nerves L5-6 induces mechanical and cold allodynia, but it does not seem to produce general suffering or measurable anxiety to the animals. Furthermore, tests for anxiety and depression were not able to predict which animals were vulnerable to express symptoms of neuropathic pain after nerve injury.