Pain
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Comparative Study
The putative cannabinoid receptor GPR55 plays a role in mechanical hyperalgesia associated with inflammatory and neuropathic pain.
It has been postulated that the G protein-coupled receptor, GPR55, is a third cannabinoid receptor. Given that the ligands at the CB(1) and CB(2) receptors are effective analgesic and anti-inflammatory agents, the role of GPR55 in hyperalgesia associated with inflammatory and neuropathic pain has been investigated. As there are no well-validated GPR55 tool compounds, a GPR55 knockout (GPR55(-/-)) mouse line was generated and fully backcrossed onto the C57BL/6 strain. ⋯ This suggests that GPR55 signalling can influence the regulation of certain cytokines and this may contribute to the lack of inflammatory mechanical hyperalgesia in the GPR55(-/-) mice. In the model of neuropathic hypersensitivity, GPR55(-/-) mice also failed to develop mechanical hyperalgesia up to 28 days post-ligation. These data clearly suggest that the manipulation of GPR55 may have therapeutic potential in the treatment of both inflammatory and neuropathic pain.
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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.
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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.
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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.
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Randomized Controlled Trial Comparative Study
Spinal cord stimulation normalizes abnormal cortical pain processing in patients with cardiac syndrome X.
Cardiac syndrome X (CSX) is characterized by effort angina, ST-segment depression during stress tests and normal coronary arteries. Abnormal nociception was suggested in these patients by studies showing a reduced cardiac pain threshold; furthermore, we recently found a lack of habituation to pain stimuli using recording of laser evoked potentials (LEPs). In CSX patients with severe angina, spinal cord stimulation (SCS) was shown to improve symptoms. ⋯ Similar results were observed during right-hand stimulation. Our study shows that in CSX patients SCS is able to restore habituation to peripheral pain stimuli. This effect might contribute to restore the ability of CSX patients to better tolerate cardiac pain.