The journal of pain : official journal of the American Pain Society
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Anecdotally, orofacial pain patients sometimes report that the painful face area feels "swollen." Because there are no clinical signs of swelling, such illusions may represent perceptual distortions. In this study, we examine whether nociceptive stimulation can lead to perceptual distortion of the face in a way similar to that of local anesthesia. Sixteen healthy participants received injections of .4 mL hypertonic saline to induce short-term nociceptive stimulation, .4 mL mepivacaine (local anesthetic) to transiently block nerve transduction, and .4 mL isotonic saline as a control condition. Injections were administered in both the infraorbital and the mental nerve regions. Perceptual distortions were conceptualized as perceived changes in magnitude of the injected areas and the lips, and they were measured using 1) a verbal subjective rating scale and 2) a warping procedure. Prior to the study, participants filled in several psychological questionnaires. This study shows that both nociceptive stimulation (P < .05) and transient blocking of nerve transduction (P < .05) can lead to perceptual distortion of the face. A test-retest experiment including 9 new healthy subjects supported the results. Perceptual distortions were positively correlated with the psychological variable of dissociation in several conditions (P < .05). Perceptual distortions may therefore be influenced by somatosensory changes and psychological mechanisms. ⋯ Knowledge of the factors that influence the perception of the face is important to understand the possible implications of perceptual distortions in orofacial pain disorders (and possibly other chronic pain states). Such information may ultimately open up new avenues of treatment for persistent orofacial pain.
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Current research on the risk of opioid analgesics with drug overdose does not account for the total morphine equivalent dose (MED) of opioids filled by a patient. In this study, time from first opioid prescription until drug overdose was examined for 206,869 privately insured patients aged 18 to 64 with noncancer pain and ≥2 filled prescriptions for Schedule II or III opioids from January 2009 to July 2012. Opioid therapy was examined in 6-month intervals including 6 months before an overdose and categorized as mean daily MED (0, 1-19, 20-49, 50-99, ≥100 mg) and total MED divided at top quartile (0, 1-1,830, >1,830 mg). Survival analysis was used, adjusting for demographics, clinical conditions, and psychoactive drugs. Relative to no opioid therapy, persons at highest risk for overdose (adjusted hazard ratios of 2-3) received a daily MED of ≥100 mg regardless of total dose or a daily MED of 50 to 99 mg with a high total MED (>1,830 mg). The hazard ratio was significantly lower (1.43, 95% confidence interval = 1.15-1.79) for 50 to 99 mg daily MED with a lower total MED (≤1,830 mg), whereas hazard ratios for lower daily MEDs did not differ by total dose. This analysis suggests that clinicians should consider total MED to assess risk of overdose for persons prescribed 50 to 99 mg daily MED. ⋯ When addressing risks for drug overdose, this analysis supports the need for clinicians, administrators, and policy makers to monitor not only daily opioid dose but also total dose for patients receiving 50 to 99 mg daily MED.
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Vocalizing is a ubiquitous pain behavior. The present study investigated whether it helps alleviate pain and sought to discern potential underlying mechanisms. Participants were asked to immerse one hand in painfully cold water. On separate trials, they said "ow," heard a recording of them saying "ow," heard a recording of another person saying "ow," pressed a button, or sat passively. Compared to sitting passively, saying "ow" increased the duration of hand immersion. Although on average, participants predicted this effect, their expectations were uncorrelated with pain tolerance. Like vocalizing, button pressing increased the duration of hand immersion, and this increase was positively correlated with the vocalizing effect. Hearing one's own or another person's "ow" was not analgesic. Together, these results provide first evidence that vocalizing helps individuals cope with pain. Moreover, they suggest that motor more than other processes contribute to this effect. ⋯ Participants immersed their hand in painfully cold water longer when saying "ow" than when doing nothing. Whereas button pressing had a similar effect, hearing one's own or another person's "ow" did not. Thus, vocalizing in pain is not only communicative. Like other behaviors, it helps cope with pain.
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Chronic pruritic conditions are often associated with dry skin and loss of epidermal barrier integrity. In this study, repeated application of acetone and ether followed by water (AEW) to the cheek skin of mice produced persistent scratching behavior with no increase in pain-related forelimb wiping, indicating the generation of itch without pain. Cheek skin immunohistochemistry showed a 64.5% increase in total epidermal innervation in AEW-treated mice compared to water-treated controls. This increase was independent of scratching, because mice prevented from scratching by Elizabethan collars showed similar hyperinnervation. To determine the effects of dry skin treatment on specific subsets of peripheral fibers, we examined Ret-positive, calcitonin gene-related peptide (CGRP)-positive, and glial cell line-derived neurotrophic factor family receptor α3 (GFRα3)-positive intraepidermal fiber density. AEW treatment increased Ret-positive fibers but not CGRP-positive or GFRα3-positive fibers, suggesting that a specific subset of nonpeptidergic fibers could contribute to dry skin itch. To test whether trigeminal ganglion neurons innervating the cheek exhibited altered excitability after AEW treatment, primary cultures of retrogradely labeled neurons were examined using whole-cell patch clamp electrophysiology. AEW treatment produced no differences in measures of excitability compared to water-treated controls. In contrast, a significantly higher proportion of trigeminal ganglion neurons was responsive to the nonhistaminergic pruritogen chloroquine after AEW treatment. We conclude that nonpeptidergic, Ret-positive fibers and chloroquine-sensitive neurons may contribute to dry skin pruritus. ⋯ This study examines the underlying neurobiological mechanisms of persistent dry skin itch. Our results indicate that nonpeptidergic epidermal hyperinnervation and nonhistaminergic pruritic receptors are potential targets for chronic pruritus.