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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...
Recent studies have indicated that metabotropic glutamate receptors mGluR5, mGluR2/3 and mGluR7 are present in the regions of central nervous system important for nociceptive transmission, but their involvement in neuropathic pain has not been well established. We demonstrated that acute and chronic administration of MPEP (mGluR5 antagonist), LY379268 (mGluR2/3 agonist), and AMN082 (mGluR7 agonist)...
Keratinocytes are implicated in sensory transduction and can influence nociception, but whether these contribute to chronic pain is not known. In neurons, voltage-gated sodium channels (Na v ) are involved in neuropathic pain and are activated by depolarization. Since keratinocytes can also show changes in membrane potential, we used RT-PCR, in situ hybridization, and immunohistochemistry...
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...
The role of prostanoids in nociception is well established. The headache eliciting effects of prostacyclin (prostaglandin I 2 , (PGI 2 )) and its possible mechanisms had previously not been systematically studied in man. We hypothesized that infusion of PGI 2 might induce headache and vasodilatation of cranial vessels. A stable analog of PGI 2 epoprostenol (10ng/kg/min)...
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. Furthermore, 79% of male and 85% of female prescription opioid abusers indicated...
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. μ-Opioid receptor (μOR, 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...
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...
The length of the reporting period specified for items assessing pain and fatigue varies among instruments. How the length of recall impacts the accuracy of symptom reporting is largely unknown. This study investigated the accuracy of ratings for reporting periods ranging from 1 day to 28 days for several items from widely used pain and fatigue measures (SF36v2, Brief Pain Inventory, McGill Pain Questionnaire,...
Transient receptor potential vanilloid 1 (TRPV1) is highly expressed in primary afferent neurons. Tissue damage generates an array of chemical mediators that activate and sensitize afferent nerve fibers, and sensitization of afferent nerve fibers plays an important role in development of visceral pain. We investigated participation of TRPV1 in visceral pain associated with bladder inflammation induced...
The fear avoidance model (FAM) postulates that fear of pain or reinjury is a risk factor for persistent pain and disability, because it leads to the avoidance of physical activity. Research on the FAM has not yielded consistent results, which may be attributed to the model itself, but could also be a product of the way fear of movement is assessed. Studies of the FAM have measured fear using verbal...
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. The patients had no signs of neuropathy except cold allodynia. We applied 20% cinnamaldehyde...
Low back pain (LBP) is common among adolescents and it has been estimated that one-fifth of adolescents suffer from recurrent severe LBP. However, longitudinal studies describing the risk factors of LBP are scarce. The purpose of this study was to investigate whether health, physical activity and other health behaviors, socio-demographic background and school success predict LBP hospitalization until...
Chronic abdominal pain is a common gastrointestinal symptom experienced by patients. We have previously shown that IBS patients with visceral hypersensitivity also have evidence of thermal hypersensitivity of the hand and foot that is reversed by rectal lidocaine jelly. We have also recently developed an animal model of chronic visceral and somatic hypersensitivity in rats treated with intracolonic...
The rostral ventromedial medulla (RVM) is an area of the brainstem involved in the descending modulation of nociception at the level of the spinal cord. Although the RVM is involved in the inhibition or facilitation of nociception, the underlying mechanisms are not understood. Here we examined the role of the neuropeptide substance P and neurokinin-1 (NK-1) receptors located in the RVM on withdrawal...
Intrinsic excitability (IE) can be defined as an output of action potentials from a given input signal. Changes to the IE of a neuron are an important aspect of the cellular plasticity that underlies learning and memory process. In this study, long-term plastic change in IE of deep dorsal horn neurons (DHNs) was investigated. Associative spike pairing stimulation (PS) induced a long-lasting increase...
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