The journal of pain : official journal of the American Pain Society
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Evidence suggests an important role for supraspinal gamma-aminobutyric acid (GABA) in conditioned fear and pain. Using dual probe microdialysis coupled to HPLC, we investigated alterations in extracellular levels of GABA simultaneously in the rat basolateral amygdala and dorsal periaqueductal gray during expression of conditioned fear, formalin-evoked nociception, and fear-conditioned analgesia. Re-exposure to a context previously paired with footshock significantly increased the duration of freezing and 22-kilohertz ultrasonic vocalization, and reduced formalin-evoked nociceptive behavior. Upon re-exposure to the context, GABA levels in the basolateral amygdala were significantly lower in fear-conditioned animals compared with non-fear-conditioned controls, irrespective of intraplantar formalin/saline injection. GABA levels in the dorsal periaqueductal gray were lower in rats receiving intraplantar injection of formalin, compared with saline-treated controls. GABA levels sampled were sensitive to nipecotic acid and calcium infusion. No specific fear-conditioned analgesia-related alterations in GABA efflux were observed in these regions despite the ability of rats undergoing dual probe microdialysis to express this important survival response. In conclusion, expression of contextually induced fear- and pain-related behavior are accompanied by suppression of GABA release in the basolateral amygdala and dorsal periaqueductal gray, respectively, compared with non-fear, non-pain controls. ⋯ This study investigates alterations in levels of the neurotransmitter GABA simultaneously in the rat amygdala and periaqueductal grey during expression of pain- and fear-related behavior and fear-induced analgesia. The results enhance our understanding of the role of this neurotransmitter in pain, memory of pain and control of pain during fear.
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Randomized Controlled Trial Clinical Trial
An investigation into the effects of frequency-modulated transcutaneous electrical nerve stimulation (TENS) on experimentally-induced pressure pain in healthy human participants.
Frequency-modulated transcutaneous electrical nerve stimulation (TENS) delivers currents that fluctuate between preset boundaries over a fixed period of time. This study compared the effects of constant-frequency TENS and frequency-modulated TENS on blunt pressure pain in healthy human volunteers. Thirty-six participants received constant-frequency TENS (80 pps), frequency-modulated TENS (20 to 100 pps), and placebo (no current) TENS at a strong nonpainful intensity in a randomized cross-over manner. Pain threshold was taken from the forearm using pressure algometry. There were no statistical differences between constant-frequency TENS and frequency-modulated TENS after 20 minutes (OR = 1.54; CI, 0.29, 8.23, P = 1.0). Both constant-frequency TENS and frequency-modulated TENS were superior to placebo TENS (OR = 59.5, P < .001 and OR = 38.5, P < .001, respectively). Frequency-modulated TENS does not influence hypoalgesia to any greater extent than constant-frequency TENS when currents generate a strong nonpainful paraesthesia at the site of pain. The finding that frequency-modulated TENS and constant-frequency TENS were superior to placebo TENS provides further evidence that a strong yet nonpainful TENS intensity is a prerequisite for hypoalgesia. ⋯ This study provides evidence that TENS, delivered at a strong nonpainful intensity, increases pain threshold to pressure algometry in healthy participants over and above that seen with placebo (no current) TENS. Frequency-modulated TENS does not increase hypoalgesia to any appreciable extent to that seen with constant-frequency TENS.
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The purpose of this study was to identify racial and ethnic differences in patient-reported rates of treatment for chronic pain and ratings of pain-treatment effectiveness among veterans treated in Veterans Affairs (VA) facilities. This was a cross-sectional analysis of data from 255,522 veterans who participated in the VA Survey of the Healthcare Experiences of Patients (SHEP) in Fiscal Year 2005. Measures included demographics, the Veterans Rand Health Survey-12, a single item inquiring if the patient received treatment for chronic pain in the VA within the prior 12 months, and a single item asking the patient to rate the effectiveness of chronic pain care. In a logistic model adjusting for demographics, pain interference, and mental health status, male and female veterans who were Hispanic (OR 1.39 [95%CI 1.26-1.53] and OR 1.57 [1.02-2.43], respectively) or non Hispanic black (OR 1.43 [1.33-1.54] and OR 1.35 [1.02-1.78], respectively) were more likely to report receiving treatment for chronic pain in the prior 12 months compared to non Hispanic white veterans. Among veterans who reported receiving treatment for chronic pain, non Hispanic black men were less likely to rate pain-treatment effectiveness as very good or excellent, compared to non Hispanic white men (OR .809 [.720-.910]). ⋯ In our study, Hispanic and non Hispanic black veterans reported receiving chronic pain treatment more frequently than white veterans. Among veterans reporting pain treatment, non Hispanic black men were somewhat less likely to report receiving highly effective treatment than white men. Further research is needed to understand the reasons for these differences and their potential clinical implications.
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To examine the use of extended-release (ER) opioids relative to immediate-release (IR) opioids in chronic opioid prescription episodes, pharmacy claim data from a national health plan database were analyzed. Enrollees having at least 1 pharmacy claim for an opioid formulation between June 2003 and May 2006, and at least 1 year of continuous enrollment after their first observed pharmacy claim were included. Opioid prescription episodes were created by combining contiguous days of therapy, allowing for a maximum of 7 days between refills (>or=8 d = new episode). Outcomes are reported in the form of probabilities and odds ratios (ORs). A total of 3,993,011 opioid prescription episodes were derived from 1,967,898 enrollees. Overall, prescription episodes involving IR preparations (97.7%) were more prevalent than episodes using ER preparations (2.3%). The odds of an ER preparation being prescribed chronically (>or=60 d) were approximately 11 times that of an IR preparation (OR = 10.7); however, the majority of chronic prescription episodes used IR formulations (84.8%). When stratified by prescriber type (specialist vs nonspecialists), the probability of a specialist prescribing ER opioids in these chronic prescription episodes was 19.1% versus 13.7% for nonspecialists. Specialists were about 50% more likely to prescribe ER opioids relative to nonspecialists (OR = 1.49). ⋯ This analysis suggests that the availability of pain-treatment guidelines, recommendations, and education alone may not be enough to influence opioid-prescribing practices in the treatment of chronic pain.
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Negative emotion has a variable effect on pain perception. This variability has been explained by the motivational priming hypothesis (MPH) which predicts that emotional stimuli generating low levels of arousal will facilitate pain, while stimuli generating high levels of arousal will inhibit pain. However, a study by Sneddon et al with rainbow trout discovers a relationship not found in the human literature, that fear-related behavior decreased in the presence of a nociceptive stimulus. The current experiment examined this possibility in humans. In Experiment 1, 30 healthy, female subjects with "at least a mild aversion to spiders" participated in 3 trials: 1 in which a Brazilian salmon pink tarantula was present; a second with the right hand immersed in a cold pressor; and a third with both the tarantula and the cold pressor present. Experiment 2 added distance as an extra variable to this methodology. In both experiments it was found that spider presence had no impact upon pain perception but spider fear was reduced by the cold pressor. There was no interaction between trial and either time or distance. These findings are novel in human subjects and not well accounted for by the MPH. We suggest that an explicitly evolutionary framework should be adopted, and that spider fear was reduced to facilitate escape from the more threatening cold-pressor experience. ⋯ This study examined the relationship between pain and fear. Subjects with an aversion to spiders sat next to a tarantula with their right hand in iced water. Subjects reported reduced fear but no change in pain. Consequently, the authors reevaluate the Motivational Priming Hypothesis and emphasize evolutionarily determined threat values.