Pain
-
Editorial Comment
An SCN9A variant, known to cause pain, is now found to cause itch.
-
The amygdala is a key brain region with efferent and afferent neural connections that involve complex behaviors such as pain, reward, fear, and anxiety. This study evaluated resting state functional connectivity of the amygdala with cortical and subcortical regions in a group of chronic pain patients (pediatric complex regional pain syndrome) with age-sex matched control subjects before and after intensive physical-biobehavioral pain treatment. Our main findings include (1) enhanced functional connectivity from the amygdala to multiple cortical, subcortical, and cerebellar regions in patients compared with control subjects, with differences predominantly in the left amygdala in the pretreated condition (disease state); (2) dampened hyperconnectivity from the left amygdala to the motor cortex, parietal lobe, and cingulate cortex after intensive pain rehabilitation treatment within patients with nominal differences observed among healthy control subjects from time 1 to time 2 (treatment effects); (3) functional connectivity to several regions key to fear circuitry (prefrontal cortex, bilateral middle temporal lobe, bilateral cingulate, hippocampus) correlated with higher pain-related fear scores; and (4) decreases in pain-related fear associated with decreased connectivity between the amygdala and the motor and somatosensory cortex, cingulate, and frontal areas. Our data suggest that there are rapid changes in amygdala connectivity after an aggressive treatment program in children with chronic pain and intrinsic amygdala functional connectivity activity serving as a potential indicator of treatment response.
-
Candidate gene studies have revealed limited genetic bases for opioid analgesic response variability. Genome-wide association studies facilitate impartial queries of common genetic variants, allowing identification of novel genetic contributions to drug effect. Illumina (Illumina Inc, San Diego, CA, USA) single nucleotide polymorphism (SNP) arrays were used to investigate SNP associations with total morphine requirement as a quantitative trait locus and with postoperative pain in a retrospective population of opioid-naïve children ages 4-18years who had undergone day surgery tonsillectomy and adenoidectomy. ⋯ No association with morphine dose was detected in African Americans (AA) (n=241). Postoperative pain scores ≥ 7/10 were associated with rs795484 (G>A) in the EC cohort (odds ratio 2.35, 95% CI 1.56-3.52, P<0.00005) and this association replicated in AA children (odds ratio 1.76, 95% CI 1.14-2.71, P<0.01). Variants in TAOK3 encoding the serine/threonine-protein kinase, TAO3, are associated with increased morphine requirement in children of EC ancestry and with increased acute postoperative pain in both EC and AA subjects.
-
The evidence on the patterns of nonsteroidal anti-inflammatory drug (NSAID) use according to pain prevalence and clinical guidelines in older people is sparse. This cross-sectional study examined the patterns of NSAID use according to pain prevalence and concordance with clinical guideline recommendations for safe NSAID use in older people, in relation to duration of use, patterns of use, concomitant use of proton pump inhibitors (PPIs), and prevalence of specific drug interactions. Community-dwelling men (n=1696) age ≥ 70 years living in Sydney were studied. 8.2% (n=139) of participants reported regular NSAID use compared with 2.9% (n=50) reporting as-needed use. ⋯ In relation to pain prevalence, regular NSAID users were significantly more likely to report chronic pain (P<.0001), recent pain (P=.0001), and chronic intrusive pain (P<.0001) compared with nonregular users. The findings of this study indicate that NSAID prescribing practices do not align with clinical guidelines for safe use in older people. This difference between the guideline recommendations and what is happening in the real world should be explored further.
-
Extracellular high mobility group box-1 protein (HMGB1) plays important roles in the pathogenesis of nerve injury- and cancer-induced pain. However, the involvement of spinal HMGB1 in arthritis-induced pain has not been examined previously and is the focus of this study. Immunohistochemistry showed that HMGB1 is expressed in neurons and glial cells in the spinal cord. ⋯ Furthermore, the pro-nociceptive effect of i.t. injection of HMGB1 persisted in Tlr2- and Rage-, but was absent in Tlr4-deficient mice. The same pattern was observed for HMGB1-induced spinal microglia and astrocyte activation and cytokine induction. These results demonstrate that spinal HMGB1 contributes to nociceptive signal transmission via activation of TLR4 and point to disulfide HMGB1 inhibition as a potential therapeutic strategy in treatment of chronic inflammatory pain.