Mol Pain
-
Genetic variation contributes to differences in pain sensitivity and response to different analgesics. Catecholamines are involved in the modulation of pain and are partly metabolized by the catechol-O-methyltransferase (COMT) enzyme. Genetic variability in the COMT gene may therefore contribute to differences in pain sensitivity and response to analgesics. It is shown that a polymorphism in the COMT gene, Rs4680 (Val158Met), influence pain sensitivity in human experimental pain and the efficacy for morphine in cancer pain treatment. In this study we wanted to investigate if variability in other regions in the COMT gene also contributes to interindividual variability in morphine efficacy. ⋯ This study suggests that genetic variability in the COMT gene influence the efficacy of morphine in cancer patients with pain, and that increased understanding of this variability is reached by expanding from analyses of single SNPs to haplotype construction and analyses.
-
The laterocapsular division of the central nucleus of the amygdala (CeLC) has emerged as an important site of pain-related plasticity and pain modulation. Glutamate and neuropeptide receptors in the CeLC contribute to synaptic and behavioral changes in the arthritis pain model, but the intracellular signaling pathways remain to be determined. This study addressed the role of PKA, PKC, and ERK in the CeLC. ⋯ Administration of KT5720 (100 microM, concentration in microdialysis probe) or U0126 (100 microM) into the CeLC, but not striatum (placement control), inhibited audible and ultrasonic vocalizations and spinal reflexes of arthritic rats but had no effect in normal animals. GF109203x (100 microM) and U0124 (100 microM) did not affect pain behavior. The data suggest that in the amygdala PKA and ERK, but not PKC, contribute to pain-related synaptic facilitation and behavior by increasing NMDA receptor function through independent signaling pathways.
-
The chronic use of opioids prior to surgery leads to lowered pain thresholds and exaggerated pain levels after these procedures. Several mechanisms have been proposed to explain this heightened sensitivity commonly termed opioid-induced hyperalgesia (OIH). Most of these proposed mechanisms involve plastic events in the central or peripheral nervous systems. Alterations in the abundance of peripheral mediators of nociception have not previously been explored. ⋯ The enhanced level of nociceptive sensitization seen after incision in animals chronically exposed to morphine is associated with elevated levels of several cytokines previously reported to be relevant to this incisional pain model. The cytokines may be functional in supporting nociceptive sensitization because pentoxifylline reverses both peri-incisional skin cytokine levels and OIH. Opioid administration beginning at the time of incision does not seem to have the same cytokine enhancing effect. Approaches to postoperative pain control involving a reduction of cytokines may be an effective way to control excessive pain in patients chronically using opioids prior to surgical procedures.
-
The effects of an analgesic treatment (lidocaine patches) on brain activity in chronic low back pain (CBP) and in knee osteoarthritis (OA) were investigated using serial fMRI (contrasting fMRI between before and after two weeks of treatment). Prior to treatment brain activity was distinct between the two groups: CBP spontaneous pain was associated mainly with activity in medial prefrontal cortex, while OA painful mechanical knee stimulation was associated with bilateral activity in the thalamus, secondary somatosensory, insular, and cingulate cortices, and unilateral activity in the putamen and amygdala. ⋯ We conclude that the two chronic pain conditions involve distinct brain regions, with OA pain engaging many brain regions commonly observed in acute pain. Moreover, lidocaine patch treatment modulates distinct brain circuitry in each condition, yet in OA we observe divergent results with fMRI and with questionnaire based instruments.
-
Resiniferatoxin (RTX) is an ultrapotent capsaicin analog that binds to the transient receptor potential channel, vanilloid subfamily member 1 (TRPV1). There is a large body of evidence supporting a role for TRPV1 in noxious-mediated and inflammatory hyperalgesic responses. In this study, we evaluated low, graded, doses of perineural RTX as a method for regional pain control. ⋯ Using a range of mechanical and thermal algesic tests, we found that the most sensitive measure following perineural RTX administration was inhibition of inflammatory hyperalgesia. Recovery studies showed that physiologic sensory function could return as early as two weeks post-RTX treatment, however, immunohistochemical examination of the DRG revealed a partial, but significant reduction in the number of the TRPV1-positive neurons. We propose that this method could represent a beneficial treatment for a range of chronic pain problems, including neuropathic and inflammatory pain not responding to other therapies.