The journal of pain : official journal of the American Pain Society
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The objective of the present study was to evaluate the time course of changes in peripheral nerve insulin receptor (IR) signaling and compare observed findings with behavioral responses to noxious mechanical and thermal stimuli in streptozotocin (STZ)-diabetic rats over 12 weeks of diabetes. Diabetic rats developed mechanical hyperalgesia, as indicated by decreased paw withdrawal thresholds to mechanical stimuli that were detectable after 2 weeks of diabetes; they also developed thermal hypoalgesia, as indicated by increased tail flick latencies to thermal stimuli that were detectable at 1 week of diabetes. Western blot analysis revealed decreased phosphorylated: total IR protein ratio that was detectable as early as 2 weeks of diabetes, whereas phosphorylated:total Akt protein ratio was decreased at 2 weeks and increased at 12 weeks of diabetes with unchanged PI-3K protein levels. To our knowledge, the present study is the first to demonstrate that impaired peripheral nerve IR signaling, as indicated by decreased phosphorylated:total IR protein ratio, coincides with early mechanical hyperalgesia and thermal hypoalgesia in STZ-diabetic rats. This finding may improve understanding of how altered pain sensation develops rapidly in this model. ⋯ This study examined peripheral nerve IR signaling during the early course of altered nociception in STZ-diabetic rats. In diabetic rats, impaired peripheral nerve IR signaling is observed shortly after STZ injection, as is altered nociception. This finding suggests a possible role of impaired IR signaling in diabetic sensory neuropathy.
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We have recently demonstrated that inferior alveolar nerve and mental nerve (branches of the mandibular nerve) injury from rats serves as a valid trigeminal neuropathic pain model. In these animals, we found that neuronal loss of trigeminal ganglion (TG) was not correlated with pain hypersensitivity. In this study, we examined changes of transient receptor potential vanilloid 1 (TRPV1) expression in the injured and uninjured TG neurons using immunohistochemical analysis at 3 days after surgery, the time point where we observed significant pain hypersensitivity. Injured neurons were identified by positive immunoreactivity for activating transcription factor 3 (ATF3). ATF3 immunoreactivity was exclusively observed in the nuclei of subpopulation of ipsilateral mandibular TG neurons, whereas no ATF3 expression was found in the naive and contralateral TG neurons. Interestingly, the expression of TRPV1 was increased in the uninjured ipsilateral maxillary TG neurons as well as in the uninjured ipsilateral mandibular TG neurons. The upregulation of TRPV1 and ATF3 expression returned to the basal level at 60 days after surgery. Our results demonstrate that trigeminal sensory nerve injury induced differential changes in TRPV1 expression of the injured and uninjured TG neurons. The upregulation of TRPV1 in uninjured TG neurons may play an important role in pain hypersensitivity after trigeminal nerve injury. ⋯ The TRPV1 is a well-known pain transducer molecule and plays crucial roles in the perception of inflammatory and thermal pain. This article presents that TRPV1 expression was increased in uninjured neurons rather than injured neurons after peripheral nerve injury. The upregulation of TRPV1 in uninjured neurons may be associated with the development of neuropathic pain. TRPV1 might be a potential target for the treatment of neuropathic pain.
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Little is known about how a child's experience of pain affects his or her parents. Using a vignette methodology, this study investigated the emotional responses of parents who were asked to imagine different painful situations that their child might experience. A sample of 650 parents of school children (325 mothers; 325 fathers) read 8 short stories/vignettes about their child, which varied in terms of type of situation (pain vs other stressful situation), intensity (high vs low), and frequency of occurrence (high vs low). The role of individual differences in parental catastrophizing about their child's pain, catastrophizing about their own pain, dispositional empathy, and gender was also investigated. Parents' dispositional empathy was found to have an impact on parental distress and concern for their child. Catastrophizing about their child's pain had a unique contribution to parents' emotional responses to the vignettes describing their child in pain, beyond the influence of other variables. The impact of parental catastrophizing about their child's pain was most pronounced for parental distress, probably reflecting the high threat value that they attribute to their child's pain. The findings are discussed within recent models of empathy and pain, delineating possible relationships with parents' behavioral responses to their child's pain. ⋯ This vignette study found preliminary evidence for the importance of parent characteristics, beyond situational characteristics, in parental emotional responses to their child's pain. The findings provide indications for the processes implied in parental helping behavior.
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Randomized Controlled Trial Multicenter Study Clinical Trial
Efficacy of dronabinol as an adjuvant treatment for chronic pain patients on opioid therapy.
We assessed the efficacy of dronabinol (Marinol capsules; Solvay Pharmaceuticals, Brussels, Belgium), a synthetic Delta(9)-THC (tetrahydrocannabinol), in 30 patients taking opioids for chronic pain to determine its potential analgesic effects as an adjuvant treatment. Phase I of this 2-phase study was a randomized, single-dose, double-blinded, placebo-controlled, crossover trial in which subjects were randomly administered either 10 mg or 20 mg of dronabinol or identical placebo capsules over the course of three, 8-hour visits. Baseline self-report measures, hourly ratings of pain intensity, pain relief, pain bothersomeness, treatment satisfaction, mood, side effects, and blood serum levels were obtained. Phase II was an extended open-label titrated trial of dronabinol as add-on medication to patients on stable doses of opioids. Results of the Phase I study showed that patients who received dronabinol experienced decreased pain intensity and increased satisfaction compared with placebo. No differences in benefit were found between the 20 mg and 10 mg doses. In the Phase II trial, titrated dronabinol contributed to significant relief of pain, reduced pain bothersomeness, and increased satisfaction compared with baseline. The incidence of side effects was dose-related. Overall, the use of dronabinol was found to result in additional analgesia among patients taking opioids for chronic noncancer pain. ⋯ This study examines the effect of adding a cannabinoid to the regimen of patients with chronic pain who report significant pain despite taking stable doses of opioids. The results of our preliminary study suggest that dronabinol, a synthetic THC, may have an additive effect on pain relief.
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Two lines of evidence about the association between the experience of pain and brain state (measured via electroencephalogram or EEG) have recently come to light. First, research from a number of sources suggests a link between brain EEG activity and the experience of pain. Specifically, this research suggests that the subjective experience of pain is associated with relatively lower amplitudes of slower wave (delta, theta, and alpha) activity and relatively higher amplitudes of faster wave (beta) activity. Second, there has been a recent increase in interest in interventions that impact the cortical neuromodulation of pain, including behavioral treatments (such as self-hypnosis training and neurofeedback) and both invasive and noninvasive brain stimulation. Although a direct causal link between experience of pain and brain activity as measured by EEG has not been established, the targeting of pain treatment at a cortical level by trying to affect EEG rhythms directly is an intriguing possibility. ⋯ Preliminary evidence suggests the possibility, which has not yet adequately tested or proven, that the experience of chronic pain is linked to cortical activity as assessed via an electroencephalogram. Support for this hypothesis would have important implications for understanding the mechanisms that underlie a number of pain treatments, and for developing new innovative treatments for chronic pain management.