Pain
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Comparative Study
Transgene-mediated enkephalin release enhances the effect of morphine and evades tolerance to produce a sustained antiallodynic effect in neuropathic pain.
We examined the pharmacologic characteristics of herpes simplex virus (HSV) vector-mediated expression of proenkephalin in the dorsal root ganglion in a rodent model of neuropathic pain. We found that: (i). vector-mediated enkephalin produced an antiallodynic effect that was reversed by naloxone; (ii). vector-mediated enkephalin production in animals with spinal nerve ligation prevented the induction of c-fos expression in second order sensory neurons in the dorsal horn of spinal cord; (iii). the effect of vector-mediated enkephalin enhanced the effect of morphine, reducing the ED(50) of morphine 10-fold; (iv). animals did not develop tolerance to the continued production of vector-mediated enkephalin over a period of several weeks; and, (v). vector transduction continued to provide an analgesic effect despite the induction of tolerance to morphine. This is the first demonstration of gene transfer to provide an analgesic effect in neuropathic pain. The pharmacologic analysis demonstrates that transgene-mediated expression and local release of opioid peptides produce some effects that are distinct from peptide analogues delivered pharmacologically.
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Case Reports
Musculoskeletal pain in the Netherlands: prevalences, consequences and risk groups, the DMC(3)-study.
The objective of this paper was to present estimates on the prevalence of musculoskeletal pain of five different anatomical areas and ten anatomical sites, and their consequences and risk groups in the general Dutch population. Cross-sectional data from a population-based study of a sex-age stratified sample of Dutch inhabitants of 25 years and older were used. With a postal questionnaire data was assessed on musculoskeletal pain, additional pain characteristics (location, duration, course), its consequences (utilization of health care, sick leave and limitation in daily life) and general socio-demographic characteristics. ⋯ Between 33 and 42% of those with complaints consulted their general practitioner about their pain. With the exception of persons who are work disabled, general sociodemographic characteristics cannot be used to identify high risk groups. Musculoskeletal pain is common in all subgroups of the population and has far-reaching consequences for health, work and the use of health care.
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Randomized Controlled Trial Comparative Study Clinical Trial
Placebo analgesia and the heart.
Placebo-activated endogenous opioids act on pain mechanisms inducing analgesia, as well as on the respiratory centers inducing respiratory depression. Here, we show that placebo analgesia is accompanied by a reduced beta-adrenergic activity of the heart. We measured heart rate during placebo-induced expectation of analgesia, both in the clinical and the laboratory setting. ⋯ By contrast, both placebo responses were present during muscarinic blockade with atropine, indicating no involvement of the parasympathetic system. In order to better understand the effects of naloxone and propranolol, we performed a spectral analysis of the heart rate variability for the identification of the sympathetic and parasympathetic components, and found that the beta-adrenergic low frequency (0.15 Hz) spectral component was reduced during placebo analgesia, an effect that was reversed by naloxone. These findings indicate that placebo analgesia is accompanied by a complex cascade of events which affect the cardiovascular system.
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Randomized Controlled Trial Comparative Study Clinical Trial
The mu-opioid agonist remifentanil attenuates hyperalgesia evoked by blunt and punctuated stimuli with different potency: a pharmacological evaluation of the freeze lesion in humans.
Experimental pain models inducing hyperalgesia, i.e. an increased sensitivity to noxious stimuli often present in clinical pain, are important tools for studying antinociceptive drug profiles. The correct interpretation of results obtained in these models necessitates their mechanistic understanding. This study evaluated the freeze lesion, an experimental model of hyperalgesia, in humans. ⋯ Remifentanil attenuated electrical pain with greater potency for low frequency stimulation. The potency difference of remifentanil suggests that different neuronal mechanisms mediate hyperalgesia to blunt and punctuated stimulation. Absence of brush-evoked and electrical hyperalgesia is compatible with the view that mechanical hyperalgesia to blunt and punctuated stimulation of the freeze lesion is predominantly caused by a peripheral mechanism.
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There has been a surge in interest in medicinal cannabis in Canada. We conducted a questionnaire survey to determine the current prevalence of medicinal cannabis use among patients with chronic non-cancer pain, to estimate the dose size and frequency of cannabis use, and to describe the main symptoms for which relief was being sought. Over a 6-week period in mid-2001, 209 chronic non-cancer pain patients were recruited in an anonymous cross-sectional survey. ⋯ We conclude that cannabis use is prevalent among the chronic non-cancer pain population, for a wide range of symptoms, with considerable variability in the amounts used. Discussions between patients and health care providers concerning cannabis use may facilitate education and follow up, and would allow side effects and potential interactions with other medications to be monitored. Clinical trials of cannabis for chronic non-cancer pain are warranted.