Pain
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Our previous recordings from dorsal root ganglion and spinal lamina V neurons from TRPV1-mutant mice showed dramatic decreases in responses to temperatures near the activation threshold of this channel (43-49 degrees C). Somewhat unexpectedly, we only observed behavioral deficits in these mice at higher temperatures (50-58 degrees C). In the present study, we tested the hypothesis that the noxious heat-evoked pain behavior that persists in TRPV1-mutant mice reflects residual responsiveness of neurons in the superficial, but not deep, dorsal horn. ⋯ We conclude that TRPV1 is necessary for noxious heat-evoked responses of lamina V neurons, both before and after tissue injury. It is also an essential contributor to the normal activation threshold of lamina I neurons to noxious heat and for the full duration of thermal sensitization of lamina I neurons following injury. Finally, our results suggest that the processing of noxious thermal messages by neurons in lamina I involves convergent inputs from a heterogeneous population of primary afferent thermal nociceptors.
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Randomized Controlled Trial
Adjunctive self-hypnotic relaxation for outpatient medical procedures: a prospective randomized trial with women undergoing large core breast biopsy.
Medical procedures in outpatient settings have limited options of managing pain and anxiety pharmacologically. We therefore assessed whether this can be achieved by adjunct self-hypnotic relaxation in a common and particularly anxiety provoking procedure. Two hundred and thirty-six women referred for large core needle breast biopsy to an urban tertiary university-affiliated medical center were prospectively randomized to receive standard care (n=76), structured empathic attention (n=82), or self-hypnotic relaxation (n=78) during their procedures. ⋯ Pain increased significantly in all three groups (logit slopes: standard care=0.53, empathy=0.37, hypnosis=0.34; all p<0.001) though less steeply with hypnosis and empathy than standard care (p=0.024 and p=0.018, respectively). Room time and cost were not significantly different in an univariate ANOVA despite hypnosis and empathy requiring an additional professional: 46 min/161 dollars for standard care, 43 min/163 dollars for empathy, and 39 min/152 dollars for hypnosis. We conclude that, while both structured empathy and hypnosis decrease procedural pain and anxiety, hypnosis provides more powerful anxiety relief without undue cost and thus appears attractive for outpatient pain management.
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Recent evidence points to a possible overlap in the neural systems underlying the distressing experience that accompanies physical pain and social rejection (Eisenberger et al., 2003). The present study tested two hypotheses that stem from this suggested overlap, namely: (1) that baseline sensitivity to physical pain will predict sensitivity to social rejection and (2) that experiences that heighten social distress will heighten sensitivity to physical pain as well. In the current study, participants' baseline cutaneous heat pain unpleasantness thresholds were assessed prior to the completion of a task that manipulated feelings of social distress. ⋯ Additionally, for those in the social rejection conditions, greater reports of social distress were associated with greater reports of pain unpleasantness to the thermal stimuli delivered at the end of the game. These results provide additional support for the hypothesis that pain distress and social distress share neurocognitive substrates. Implications for clinical populations are discussed.
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Living with chronic pain is associated with many deleterious outcomes, including a substantially increased risk of suicide. While many general risk factors for suicidal ideation and behavior have been identified, few studies have examined pain-related factors that confer increased or decreased risk for suicidality. The present study assessed individual differences in the use of pain-related coping strategies and pain-related catastrophizing as correlates of suicidal ideation in patients with chronic pain. ⋯ Demographic and other pain-related variables such as pain severity and duration were not generally robust predictors of suicidal ideation in this sample of patients with chronic pain. These are the first findings to suggest a unique (e.g., independent of pain severity or depressive symptomatology) association between pain-coping strategies and suicide-related cognitions in the context of chronic pain. Further research in this area, including the addition of suicide prevention materials to pain-coping skills training programs, may benefit large numbers of individuals who are at elevated suicide risk as a consequence of chronic pain.
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Lidocaine-like sodium channel blocking drugs provide pain relief either by interrupting impulse conduction in neurons when applied locally in high concentrations or, when given systemically, by suppressing high-frequency ectopic discharges due to preferential drug binding to inactivated channel states. Lidocaine-like actions of opioids have frequently been demonstrated clinically. However, drug binding to resting and inactivated channel conformations has been studied systematically only in the case of meperidine. ⋯ Sufentanil, fentanyl and tramadol but not morphine reversibly suppressed sodium inward currents at high concentrations (half-maximum blocking concentrations (IC50) 49+/-4, 141+/-6 and 103+/-8 microM) when depolarizations were started from hyperpolarized holding potentials. Short depolarizations inducing fast-inactivation and long prepulses inducing slow-inactivation significantly (*p < or = 0.001) increased the blocking potency for these opioids. 15% slow inactivated channels reduced the respective IC50 values to 5+/-3, 12+/-2 and 21+/-2 microM. These results show that: (1) Sufentanil, fentanyl and tramadol block voltage-gated sodium channels with half-maximum inhibitory concentrations similar to the IC50 reported for meperidine. (2) Slow inactivation--a physiological mechanism to suppress ectopic activity in response to slow shifts in membrane potential--increases binding affinity for sufentanil, fentanyl and tramadol. (3) Morphine has no such effects.