Pain
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Comparative Study
State-dependent block of voltage-gated Na+ channels by amitriptyline via the local anesthetic receptor and its implication for neuropathic pain.
Amitriptyline is a tricyclic antidepressant, which also alleviates various pain syndromes at its therapeutic plasma concentration (0.36-0.90 microM). Accumulated evidence suggests that such efficacy may be due to block of voltage-gated Na(+) channels. The Na(+) channel alpha-subunit protein consists of four homologous domains (D1-D4), each with six transmembrane segments (S1-S6). ⋯ The open-channel block by amitriptyline has the highest affinity, with a 50% inhibitory concentration (IC(50)) of 0.26 microM. The inactivated-channel block by amitriptyline had a weaker affinity (0.51 microM), whereas the resting-channel displayed the weakest affinity (33 microM). We hypothesize that selective block of both persistent late openings and the inactivated state of neuronal Na(+) channel isoforms by amitriptyline also occurs at its therapeutic concentration and likely contributes to its efficacy in pain syndromes.
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Comparative Study
Contributions of the anterior cingulate cortex and amygdala to pain- and fear-conditioned place avoidance in rats.
The pain experience includes a sensory-discriminative and an affective-emotional component. The sensory component of pain has been extensively studied, while data about the negative affective component of pain are quite limited. The anterior cingulate cortex (ACC), and amygdala are thought to be key neural substrates underlying emotional responses. ⋯ However, the decrease in the magnitude of S-CPA occurred only in the amygdala, but not ACC lesioned animals. Neither ACC nor amygdala lesion significantly changed formalin-induced acute nociceptive behaviors. These results suggest that the amygdala is involved in both pain- and fear-related negative emotion, and the ACC might play a critical role in the expression of pain-related negative emotion.
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Recurrent pain in childhood are common and frequently impact children's everyday functioning. However, there are currently limited tools available to measure the impact of recurrent pain on children's daily activities, in particular, that can be used to identify appropriate targets for intervention and measure response to such interventions. The purpose of this study was to develop and validate a new measure, the Child Activity Limitations Interview (CALI), to improve the assessment of functional impairment due to recurrent pain in school-age children and adolescents, and to compare this measure to the Functional Disability Inventory. ⋯ One-month test-retest reliability (r = 0.33, child report) and cross-informant reliability (r = 0.43) were moderate. Results demonstrate support for face, construct, and concurrent validity as well as responsiveness to pain symptom fluctuation. Findings demonstrate that the CALI is a promising measure for assessing and monitoring subjective report of functional impairment in school-age children and adolescents with recurrent and chronic pain.
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Relationship between changes in coping and treatment outcome in patients with Fibromyalgia Syndrome.
The present study utilized a sample of 198 individuals with Fibromyalgia Syndrome (FMS) to examine the association between treatment process variables (beliefs, coping strategies) and treatment outcomes (pain severity, activity level, emotional distress and life interference) related to a 4-week multidisciplinary fibromyalgia treatment program. Multiple regression analyses were utilized to evaluate these relationships pretreatment to posttreatment as well as from pretreatment to 3- and 6-month follow-ups. The results indicated that outcomes were most closely related to: (1) an increased sense of control over pain, (2) a belief that one is not necessarily disabled by FM, (3) a belief that pain is not necessarily a sign of damage, (4) decreased guarding, (5) increased use of exercise, (6) seeking support from others, (7) activity pacing and (8) use of coping self-statements. These findings are consistent with a cognitive-behavioural model of fibromyalgia, and suggest targets for therapeutic change.
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Nicotinic agonists have well-documented antinociceptive properties when administered subcutaneously or intrathecally in mice. However, secondary mild to toxic effects are observed at analgesic doses, as a consequence of the activation of the large family of differentially expressed nicotinic receptors (nAChRs). In order to elucidate the action of nicotinic agonists on spinal local circuits, we have investigated the expression and function of nAChRs in functionally identified neurons of neonate mice spinal cord. ⋯ Whereas GABA/glycine interneurons preferentially expressed alpha4alpha6beta2* nAChRs, alpha3beta2alpha7* nAChRs were preferentially expressed by CA or NK1-R expressing neurons. Recorded neurons were also classified by firing pattern, for comparison to results from single-cell RT-PCR studies. Altogether, our results identify distinct sites of action of nicotinic agonists in circuits of the dorsal horn, and lead us closer to an understanding of mechanisms of nicotinic spinal analgesia.