The journal of pain : official journal of the American Pain Society
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Neuropathic pain is a major clinical problem, and several animal models have been developed to investigate its mechanisms and its treatment. In this report, the role of the rostral ventromedial medulla (RVM) in the early events of the chronic constriction injury (CCI) model was investigated in behavioral and electrophysiological experiments. Placing the 4 CCI ligatures around the sciatic nerve induced large discharges and residual ongoing activity in spinal nociceptive neurons. Two weeks after CCI ligation, the rats showed behavioral hyperalgesia and allodynia as well as increased ongoing activity and responsiveness of spinal nociceptive neurons to innocuous and noxious stimuli. Blockade of excitatory synapses in the RVM by a kynurenate microinjection (2 nmol in 0.5 muL) 5 minutes before placement of the sciatic ligatures had no immediate effect on spinal neuronal activity but largely prevented the activation of spinal neurons. In kynurenate microinjected rats, behavioral hyperalgesia and allodynia developed slowly and incompletely, which corresponded with an incompletely developed hyperexcitability of spinal neurons. To the best of our knowledge, these results show for the first time that the initial response to nerve damage requires facilitation from the RVM. ⋯ The present and previous findings indicate that descending facilitation from brainstem nuclei critically contributes to the spinal hyperexcitability that underlies neuropathic pain. The present results indicate that this contribution begins at the very moment the nerve is damaged and should be prevented and treated accordingly.
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Randomized Controlled Trial Clinical Trial
A randomized, placebo-controlled, crossover trial of cannabis cigarettes in neuropathic pain.
The Food and Drug Administration (FDA), Substance Abuse and Mental Health Services Administration (SAMHSA), and the National Institute for Drug Abuse (NIDA) report that no sound scientific studies support the medicinal use of cannabis. Despite this lack of scientific validation, many patients routinely use "medical marijuana," and in many cases this use is for pain related to nerve injury. We conducted a double-blinded, placebo-controlled, crossover study evaluating the analgesic efficacy of smoking cannabis for neuropathic pain. Thirty-eight patients with central and peripheral neuropathic pain underwent a standardized procedure for smoking either high-dose (7%), low-dose (3.5%), or placebo cannabis. In addition to the primary outcome of pain intensity, secondary outcome measures included evoked pain using heat-pain threshold, sensitivity to light touch, psychoactive side effects, and neuropsychological performance. A mixed linear model demonstrated an analgesic response to smoking cannabis. No effect on evoked pain was seen. Psychoactive effects were minimal and well-tolerated, with some acute cognitive effects, particularly with memory, at higher doses. ⋯ This study adds to a growing body of evidence that cannabis may be effective at ameliorating neuropathic pain, and may be an alternative for patients who do not respond to, or cannot tolerate, other drugs. However, the use of marijuana as medicine may be limited by its method of administration (smoking) and modest acute cognitive effects, particularly at higher doses.
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Two issues relating to prescription opioid nonmedical use that to our knowledge have not been comprehensively addressed in the peer-reviewed literature are discussed: Motives for nonmedical use and the extent of nonmedical use of prescription opioids in other countries. The United States' national annual survey on illicit drug use in the general population (National Survey on Drug Use and Health) asks respondents whether they have used prescription opioids for nonmedical purposes but does not assess motives for such use. By not assessing motives, nonmedical users who use only for pain relief and nonmedical users who have other motives for use are grouped together, but 2 recent epidemiological studies suggest that these 2 groups may differ in a propensity to have substance use-related problems. We suggest that the survey add a question that assesses motives for nonmedical use. Regarding whether countries besides the United States have problems associated with nonmedical use of prescription opioids, after searching for epidemiological surveys and other materials potentially relevant to this issue, we were unable to determine the extent of nonmedical use of prescription opioids in other countries or draw cross-national comparisons. We suggest that more countries include specific questions about nonmedical use of prescription opioids in their national epidemiological surveys. ⋯ We believe that critical information surrounding the nonmedical use of prescription opioids is not being gathered. Such information would allow for a better understanding of the problem. We invite discussion and commentaries regarding the issues we raise to more effectively address this public health issue.
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This study describes further development of the Multidimensional Pain Readiness to Change Questionnaire (MPRCQ2), a measure of readiness to adopt a variety of pain management and coping strategies commonly taught in multidisciplinary treatment programs. Clinical samples were recruited from a Fibromyalgia Day Program (n = 139) and an Arthritis Day Program (n = 51) as well as 2 survey samples with pain resulting from either a spinal cord injury (n = 127) or an amputation (n = 120). The results indicate preliminary support for the reliability and validity of the MPRCQ2. The MPRCQ2 may be helpful in future research investigating the relationship between readiness to change pain-related coping and adoption of coping behaviors and adjustment to chronic pain. ⋯ This study describes the development of a revised version of the MPRCQ, the MPRCQ2, in 4 patient samples. The results support the reliability and validity of the MPRCQ2 in individuals with fibromyalgia syndrome, arthritis, acquired amputation, and spinal cord injury and improve on some aspects of the instrument.
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Characterization of a model of chronic orofacial hyperalgesia in the rat: contribution of NA(V) 1.8.
The purpose of this study was to develop and characterize a model of orofacial inflammatory hyperalgesia. Injection of complete Freund's adjuvant (CFA) into the upper lip/whisker pad of the rat produced significant and long-lasting thermal (> or =14 days) and mechanical (> or =28 days) hyperalgesia in the area of CFA injection. Both indomethacin and morphine, given systemically, significantly attenuated thermal hyperalgesia; the effect of morphine was shown to be opioid receptor-mediated. We also examined the contribution of the tetrodotoxin-resistant voltage-gated sodium channel Na(v)1.8 in CFA-produced orofacial mechanical hypersensitivity. Na(v)1.8 mRNA was increased > or =2.5-fold in trigeminal ganglion neurons 1 and 2 weeks after CFA treatment, and Na(v)1.8 protein was increased in the infraorbital nerve over a similar time course. The changes observed were time-dependent and had returned to baseline when examined 2 months after inflammation; there were no changes in Na(v)1.9 mRNA in trigeminal ganglion neurons after CFA treatment. In support of this, Na(v)1.8 antisense oligodeoxynucleotide treatment significantly attenuated CFA-produced mechanical hypersensitivity. These results document development of a model of inflammatory orofacial hyperalgesia, which, consistent with other reports, indicate a contribution of tetrodotoxin-resistant, voltage-gated sodium channel Na(v)1.8. ⋯ Orofacial hypersensitivity develops postoperatively as a routine course of orofacial surgery, and mechanical allodynia is characteristic of temporomandibular joint disorder. The results described in this report are novel with respect to the duration of orofacial hypersensitivity produced and suggest that pharmacological targeting of the voltage-gated sodium channel Na(v)1.8 may be useful in managing hypersensitivity.