Pain
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Hydrogen sulfide (H(2)S), an endogenous gas molecule synthesized by cystathionine-β-synthetase (CBS), is involved in inflammation and nociceptive signaling. However, the molecular and epigenetic mechanisms of CBS-H(2)S signaling in peripheral nociceptive processing remain unknown. We demonstrated that peripheral inflammation induced by intraplantar injection of complete Freund adjuvant significantly up-regulated expression of CBS at both protein and mRNA levels in rat dorsal root ganglia (DRG). ⋯ Peripheral inflammation did not alter expression of DNA methyltransferase 3a and 3b, the 2 major enzymes for DNA methylation, but led to a significant up-regulation of methyl-binding domain protein 4 and growth arrest and DNA damage inducible protein 45α, the enzymes involved in active DNA demethylation. Our findings suggest that epigenetic regulation of CBS expression may contribute to inflammatory hyperalgesia. H(2)S seems to increase TTX-resistant sodium channel current, which may be mediated by protein kinase A pathway, thus identifying a potential therapeutic target for the treatment of chronic pain.
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The objectives of this study were to examine whether (1) daily pain-related changes in physical functioning differed between happily partnered, unhappily partnered, and unpartnered female chronic pain patients, and (2) affect and pain cognitions mediated the partner status effect on pain-related changes in physical functioning. Two hundred fifty-one women with chronic pain due to osteoarthritis and/or fibromyalgia completed 30 daily electronic diaries assessing pain, affect, pain-related cognitions, and physical functioning. Patients living with a romantic partner also completed a modified version of the Locke-Wallace Marital Adjustment Scale to assess relationship satisfaction. ⋯ The impact of relationship status on pain-related changes in physical functioning was partly mediated by the pain cognitions catastrophizing and coping difficulty. These results indicate that happily partnered pain patients show less pain-related physical disability and more adaptive affective and cognitive responses to daily pain changes than do unhappily partnered and unpartnered patients. Living in a happy union may bolster the capacity of patients to sustain a sense of pain coping efficacy during pain episodes, which in turn, minimizes pain-related physical activity limitations.
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Randomized Controlled Trial
Optimism lowers pain: evidence of the causal status and underlying mechanisms.
Previous studies have demonstrated a relation between dispositional optimism and lower pain sensitivity, but the causal status of this link remains unclear. This study sought to test the causal status by experimentally inducing a temporary optimistic state by means of writing about and visualizing a future best possible self. In addition, we explored pain expectations and (situational) pain catastrophizing as possible underlying mechanisms of the link between optimism and pain. ⋯ Situational pain catastrophizing, however, did seem to mediate the relation between optimism and pain. This study is novel in that it confirms the causal status of optimism towards pain. Additionally, the results reveal that positive interventions might provide a useful alternative in reducing pain catastrophizing as an extremely relevant target in pain treatment.
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Randomized Controlled Trial
Amygdala activity contributes to the dissociative effect of cannabis on pain perception.
Cannabis is reported to be remarkably effective for the relief of otherwise intractable pain. However, the bases for pain relief afforded by this psychotropic agent are debatable. Nonetheless, the frontal-limbic distribution of cannabinoid receptors in the brain suggests that cannabis may target preferentially the affective qualities of pain. ⋯ Critically, the reduction in sensory-limbic functional connectivity was positively correlated with the difference in drug effects on the unpleasantness and the intensity of ongoing pain. Peripheral mechanisms alone cannot account for the dissociative effects of THC on the pain that was observed. Instead, the data reveal that amygdala activity contributes to interindividual response to cannabinoid analgesia, and suggest that dissociative effects of THC in the brain are relevant to pain relief in humans.
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Drug-resistant chronic cluster headache (CH) is an unremitting illness with excruciatingly severe headaches that occur several times daily. Starting in 2000, a total of 19 patients with long-lasting chronic CH, with multiple daily attacks unresponsive to all known prophylactics, received stimulation of the posterior inferior hypothalamic area ipsilateral to the pain as treatment. We report long-term follow-up (median 8.7 years, range 6-12 years) in 17 patients. ⋯ This exceptionally long follow-up shows that hypothalamic stimulation for intractable chronic CH produces long-lasting improvement in many patients. Previous experience was limited to a median of 16 months. Important new findings are as follows: stimulation is well tolerated for many years after implantation; after several years during which stimulation was necessary for relief, a persistent almost pain-free condition can be maintained when stimulation is off, suggesting that hypothalamic stimulation can change disease course; tolerance can occur after marked long-lasting improvement; and bilateral chronic CH seems to predict poor response to hypothalamic stimulation.