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.
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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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Selective activation of the peripheral cannabinoid receptor 1 (CB1R) has been shown to suppress neuropathic pain symptoms in rodents. However, relatively little is known about changes in CB1R and its endogenous ligands during development or maintenance of neuropathic pain. Using immunohistochemistry, Western blot, real-time reverse transcription polymerase chain reaction, as well as liquid chromatography/mass spectrometry, we studied the changes in CB1Rs and endocannabinoids N-arachidonoylethanolamine/anandamide (AEA) and 2-arachidonoylglycerol (2-AG) in rat lumbar (L4 and L5) dorsal root ganglia (DRG) after neuropathic pain induction (L5 spinal nerve ligation: SNL). ⋯ However, for these CB1R-ir neurons, we observe significant increases in percentage of TRPV1-ir cells in ipsilateral L4 DRG, and decreases in percentage of IB4- and CGRP-co-labeled cells in ipsilateral L5 DRG. Levels of both AEA and 2-AG increase significantly only in the ipsilateral L5 DRG. These results are consistent with the preserved analgesic effects of cannabinoids in neuropathic pain and provide a rational framework for the development of peripherally acting endocannabinoid-based therapeutic interventions for neuropathic pain.
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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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Histamine, substance P, serotonin and bradykinin were applied by iontophoresis to lesional and visually non-lesional skin of 14 patients with atopic dermatitis, and normal skin of 15 healthy volunteers. Itch could be evoked by light stroking of skin with a cotton swab (alloknesis) in all lesional skin sites, but not in non-lesional or normal skin. Substances were applied in the same skin area before and 3 h after administration of placebo or antihistamine (olopatadine hydrochloride: H1-receptor-blocker). ⋯ Histamine- and substance P-induced itch was almost completely suppressed by antihistamines, whereas bradykinin- and serotonin-induced itch was not. This suggests that substance P is a histamine-dependent pruritogen also in lesional skin under sensitized conditions but that bradykinin and serotonin are histamine-independent pruritogens in lesional skin. It is concluded that serotonin and bradykinin, classic endogenous algogens, can turn into potent histamine-independent pruritogens in lesional skin of atopic dermatitis.