The journal of pain : official journal of the American Pain Society
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Nociceptor Overexpression of NaV1.7 Contributes to Chronic Muscle Pain Induced by Early-Life Stress.
Adult rats previously submitted to neonatal limited bedding (NLB), a model of early-life stress, display muscle mechanical hyperalgesia and nociceptor hyperexcitability, the underlying mechanism for which is unknown. Since voltage-gated sodium channel subtype 7 (NaV1.7) contributes to mechanical hyperalgesia in several preclinical pain models and is critical for nociceptor excitability, we explored its role in the muscle hyperalgesia exhibited by adult NLB rats. Western blot analyses demonstrated increased NaV1.7 protein expression in L4-L5 dorsal root ganglia (DRG) from adult NLB rats, and antisense oligodeoxynucleotide (AS ODN) targeting NaV1.7 alpha subunit mRNA attenuated the expression of NaV1.7 in DRG extracts. ⋯ AS ODN knockdown of extracellular signal-regulated kinase 1/2, which enhances NaV1.7 function, also inhibited mechanical hyperalgesia in NLB rats. Our results support the hypothesis that overexpression of NaV1.7 in muscle nociceptors play a role in chronic muscle pain induced by early-life stress, suggesting that NaV1.7 is a target for the treatment of chronic muscle pain. PERSPECTIVE: We demonstrate that early-life adversity, induced by exposure to inconsistent maternal care, produces chronic muscle hyperalgesia, which depends, at least in part, on increased expression of NaV1.7 in nociceptors.
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Acute pain elicits a well-known inhibitory effect on upper limb corticomotor excitability, whereas the temporal effects of lower-limb experimental pain and pain in a remote limb are less clear. The aim of this study was to compare the temporal corticomotor excitability changes in the upper and lower limbs in response to acute upper and lower limb pain. In a cross-over design, 13 participants (age 29 ± 9 years; 12 male) attended 2 sessions where experimental pain was induced by injecting hypertonic saline into either the first dorsal interosseous (FDI) muscle or infrapatellar fat pad at the knee, inducing a short-lasting pain experience scored on a numerical rating scale (NRS). ⋯ The findings indicate a limb-specific corticomotor response to experimental pain that may be related to limb function. PERSPECTIVE: These data demonstrate the impact of acute, experimental pain on corticomotor excitability in the upper and lower limbs. This facilitates our understanding of the effect of pain on motor control of both local and distant muscles.
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Chronic pain and suicidal behavior are prevalent in adolescents. This longitudinal study examined the associations between pain symptoms and suicidal behavior in adolescents. A total of 7,072 adolescents participated in a follow-up study of behavior and health in Shandong, China. ⋯ PERSPECTIVE: This article presents the prospective associations of frequent pain symptoms with suicidal behavior in adolescents. Frequent pain was associated with a 50-70% increased risk of suicidal behavior 1 year later. The finding underscores the importance of pain assessment and treatment in comprehensive suicide prevention efforts in adolescents.
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We provide national surveillance estimates of pain chronicity, severity and impact in adult subpopulations defined by both Hispanic Ancestry and Race. Data are from 144,434 adults who completed validated questionnaires in the 2010-2017 National Health Interview Survey asking about pain status within the last 3 (N = 84,664) or 6 months (N = 59,770). Multivariable logistic regression was used to assess the relationship between pain and ethnicity/race. ⋯ While no differences were seen between White Puerto Rican and White Non-Hispanic participants for Category 3-4 pain, White Non-Hispanics had 40% lower odds of reporting HICP. Asian Non-Hispanic and Black Non-Hispanic participants had significantly lower odds of reporting Category 3-4 pain and HICP compared to White Puerto Rican participants, eg, Black Non-Hispanic participants had 26% lower odds off having Category 3-4 pain and 42% lower odds of having HICP. Perspective: By examining pain status in discrete demographic groups based on Hispanic Ancestry and Race, this report further documents substantial difference in health status among underserved populations and provides a baseline for continuing surveillance research on pain, with the eventual goal of eliminating disparities in pain assessment and treatment.
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The protease activated receptor (PAR) family is a group of G-protein coupled receptors (GPCRs) activated by proteolytic cleavage of the extracellular domain. PARs are expressed in a variety of cell types with crucial roles in homeostasis, immune responses, inflammation, and pain. PAR3 is the least researched of the four PARs, with little known about its expression and function. ⋯ Our findings suggest a complex role of PAR3 in the physiology and plasticity of nociceptors. PERSPECTIVE: We evaluated the role of PAR3, a G-protein coupled receptor, in nociception by developing a selective peptide agonist. Our findings suggest that PAR3 contributes to nociception in various contexts and plays a role in modulating the activity of other PARs.