The journal of pain : official journal of the American Pain Society
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Clinical and experimental data indicate that changes in the expression of voltage-gated sodium channels play a key role in the pathogenesis of neuropathic pain and that drugs that block these channels are potentially therapeutic. Clinical and experimental data also suggest that changes in voltage-gated sodium channels may play a role in inflammatory pain, and here too sodium-channel blockers may have therapeutic potential. The sodium-channel blockers of interest include local anesthetics, used at doses far below those that block nerve impulse propagation, and tricyclic antidepressants, whose analgesic effects may at least partly be due to blockade of sodium channels. Recent data show that local anesthetics may have pain-relieving actions via targets other than sodium channels, including neuronal G protein-coupled receptors and binding sites on immune cells. Some of these actions occur with nanomolar drug concentrations, and some are detected only with relatively long-term drug exposure. There are 9 isoforms of the voltage-gated sodium channel alpha-subunit, and several of the isoforms that are implicated in neuropathic and inflammatory pain states are expressed by somatosensory primary afferent neurons but not by skeletal or cardiovascular muscle. This restricted expression raises the possibility that isoform-specific drugs might be analgesic and lacking the cardiotoxicity and neurotoxicity that limit the use of current sodium-channel blockers. ⋯ Changes in the expression of neuronal voltage-gated sodium channels may play a key role in the pathogenesis of both chronic neuropathic and chronic inflammatory pain conditions. Drugs that block these channels may have therapeutic efficacy with doses that are far below those that impair nerve impulse propagation or cardiovascular function.
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Anxiety sensitivity (AS) or fear of anxiety sensations has been linked to childhood learning history for somatic symptoms, suggesting that parental AS may impact children's responses to pain. Using structural equation modeling, we tested a conceptual model in which parent AS predicted child AS, which in turn predicted a hypothesized latent construct consisting of children's pain intensity ratings for 3 laboratory pain tasks (cold pressor, thermal heat, and pressure). This conceptual model was tested in 211 nonclinical parent-child pairs (104 girls, 107 boys; mean age 12.4 years; 178 mothers, 33 fathers). Our model was supported in girls only, indicating that the sex of the child moderated the hypothesized relationships. Thus, parent AS was related to child laboratory pain intensity via its contribution to child AS in girls but not in boys. In girls, 42% of the effect of parent AS on laboratory pain intensity was explained via child AS. In boys, there was no clear link between parent AS and child AS, although child AS was predictive of experimental pain intensity across sex. Our results are consistent with the notion that parent AS may operate via healthy girls' own fear of anxiety symptoms to influence their responses to laboratory pain stimuli. ⋯ The present study highlights sex differences in the links among parent and child anxiety sensitivity (fear of anxiety sensations) and children's experimental pain responses. Among girls, childhood learning history related to somatic symptoms may be a particularly salient factor in the development of anxiety sensitivity and pain responsivity.
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The aim of this study was to translate and cross-culturally adapt the American version of the Coping Strategies Questionnaire (CSQ) and to test the reliability and validity of the German version (CSQ-D). The CSQ was translated and cross-culturally adapted following international guidelines. Reliability and validity were tested in 62 individuals with chronic musculoskeletal pain syndromes. For the concurrent criterion-related validity the CSQ-D scales were compared with the German Pain Coping Questionnaire (FESV-BW), and for the construct validity with the German Short Form 36 (SF-36). The translation process proceeded without major difficulties. In testing for reliability, the CSQ-D as a whole had a Cronbach's alpha of .94 and an intraclass correlation coefficient of .89 (95% CI .86-.98). The total CSQ-D score was correlated to the FESV-BW scales with scores of r = 0.32-0.55 and with the SF-36 Mental Component Summary with scores of r = 0.32-0.53. The CSQ-D is a precisely translated and highly reliable instrument in the assessment of chronic pain coping strategies. Its concurrent criterion-related validity and construct validity are low. The main reason for the low level of agreement between the CSQ-D and the FESV-BW was revealed by factor analysis. ⋯ This paper presents the German version of the Coping Strategies Questionnaire (CSQ-D) together with the results of clinimetric testing. The CSQ-D is a feasible and reliable outcome measure to be used in trials with German-speaking patients or large multicenter multinational trials to assess pain coping strategies in patients with chronic musculoskeletal pain.
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This study examined effects of age (young rats, approximately 35 days, vs mature rats, approximately 75-110 days) on spinal nerve ligation (SNL)-induced tactile allodynia and phosphorylation of p38 (as measured by phospho-p38 MAP kinase [P-p38]) in dorsal root ganglia and spinal cord. Effects of SNL combined with spinal nerve transection also were assessed. Mature rats displayed milder SNL-induced allodynia than young rats. Addition of spinal nerve transection distal to the ligation in older animals resulted in an allodynia comparable to that seen in young animals. In DRG, both groups displayed early (5 h) and late (10 days) peaks in P-p38 following surgery as compared to naïve rats. Tight nerve ligation plus transection had no additional effect on P-p38 levels in DRG. In spinal cord, young rats had increased levels of P-p38 from 5 h to 3 days after SNL. Phosphorylated p38 levels then decreased, with a second peak at 10 days. In contrast, spinal cord from mature rats showed less early p38 phosphorylation, although they also displayed a late 10-day peak. Addition of a transection to the ligation produced restoration of the early peak along with intensification of allodynia. Alterations of spinal P-p38 at early time points thus seem to covary with intensity of tactile allodynia. ⋯ Age and modifications to spinal nerve ligation, a common model of neuropathic pain, influence spinal p38 phosphorylation and allodynia. Early levels of spinal P-p38 seem to covary with allodynia intensity. This may mean that small variations of an injury could affect the therapeutic window of a p38 antagonist.