Pain
-
Comparative Study
Cholinergic mechanisms involved in the pain relieving effect of spinal cord stimulation in a model of neuropathy.
The mechanisms underlying the pain relieving effect of spinal cord stimulation (SCS) on neuropathic pain remain unclear. We have previously demonstrated that suppression of tactile hypersensitivity produced by SCS may be potentiated by i.t. clonidine in a rat model of mononeuropathy. Since the analgesic effect of this drug is mediated mainly via cholinergic mechanisms, a study exploring the possible involvement of the spinal cholinergic system in SCS was undertaken. ⋯ In another group of rats it was found that the response to SCS was completely eliminated by i.t. atropine and a muscarinic M(4) receptor antagonist while a partial attenuation was produced by M(1) and M(2) antagonists. Blocking of nicotinic receptors did not influence the SCS effect. In conclusion, the attenuating effect of SCS on pain related behavior is associated with the activation of the cholinergic system in the dorsal horn and mediated via muscarinic receptors, particularly M(4,) while nicotinic receptors appear not to be involved.
-
Randomized Controlled Trial Comparative Study
Genetic variability of the mu-opioid receptor influences intrathecal fentanyl analgesia requirements in laboring women.
Labor initiates one of the most intensely painful episodes in a woman's life. Opioids are used to provide analgesia with substantial interindividual variability in efficacy. mu-Opioid receptor (muOR, OPRM1) genetic variants may explain differences in response to opioid analgesia. We hypothesized that OPRM1 304A/G polymorphism influences the median effective dose (ED(50)) of intrathecal fentanyl via combined spinal-epidural for labor analgesia. ⋯ RA confirmed that 304A homozygosity significantly increases intrathecal fentanyl ED(50) (27.4 microg in Group A and 12.8 microg in Group G [p<0.002; 2.1-fold]). We demonstrate for the first time that the muOR 304G variant significantly reduces intrathecal fentanyl ED(50) for labor analgesia, suggesting women with the G variant may be more responsive to opioids and require less analgesic drugs. These findings for intrathecal fentanyl pharmacogenetics may have implications for patients receiving opioids in other settings.
-
Randomized Controlled Trial Comparative Study
Role of TRPM8 and TRPA1 for cold allodynia in patients with cold injury.
Local cold injury often induces hypersensitivity to cold and cold allodynia. Sensitisation of TRPM8 or TRPA1 could be the underlying mechanisms. This was evaluated by psychophysics and axon-reflex-flare induction following topical menthol and cinnamaldehyde application in cold injury patients and healthy subjects. ⋯ No evidence for sensitisation of responses to TRPM8 or TRPA1-stimulation was found in patients with cold injury-induced cold allodynia. The lack of TRPM8 induced axon-reflex indicates that also de-novo expression of TRPM8 on mechano-insensitive C-nociceptors does not underlie cold allodynia in these patients. We conclude from these data that the mechanisms for the induction of cold allodynia in the patients with cold injury are independent of TRPM8 or TRPA1 and differ therefore from neuropathic pain patients.
-
Randomized Controlled Trial Comparative Study
Cytokine profile in human skin in response to experimental inflammation, noxious stimulation, and administration of a COX-inhibitor: a microdialysis study.
Animal studies have documented a critical role for cytokines in cell signaling events underlying inflammation and pain associated with tissue injury. While clinical reports indicate an important role of cytokines in inflammatory pain, methodological limitations have made systematic human studies difficult. This study examined the utility of a human in vivo bioassay combining microdialysis with multiplex immunoassay techniques for measuring cytokine arrays in tissue. ⋯ These results support the utility of explored method for tracking cytokines in human tissue and suggest that anti-hyperalgesic and anti-inflammatory effects of ibuprofen are at least partially dissociated. The data further suggest that high clinical doses of ibuprofen exert anti-inflammatory effects by down-regulating tissue cytokine levels. Explored human bioassay is a promising tool for studying the pathology and pharmacology of inflammatory and chronic pain conditions.
-
Multicenter Study Comparative Study
Co-morbid pain and psychopathology in males and females admitted to treatment for opioid analgesic abuse.
The purpose of this study was to identify co-morbidity in a national sample (N=1408) of males and females entering treatment for opioid abuse. Our sample was primarily white, lived in small urban, suburban or rural locations (80%), and was well-educated. Chronic pain was a symptomatic feature in over 60% of all subjects. ⋯ Finally, most of the sample had sought treatment 3 or more times for substance abuse prior to the treatment admission in which the survey was completed. Physical and mental health were very poor in both male and female prescription opioid abusers, but females were more ill and dysfunctional than males in all physical and particularly emotional domains. Our results suggest that a small number of "at risk" opioid naive pain patients, who might abuse their therapeutically appropriate opioid analgesics, can be identified by assessing pre- and co-morbid substance abuse and significant psychopathology.