Pain
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Multicenter Study
Rapid identification and clinical indices of fear-avoidance in youth with chronic pain.
Pain-related fear and avoidance are increasingly demonstrated to play an important role in adult and childhood chronic pain. The Fear of Pain Questionnaire for Children (FOPQC) is a 24-item measure of pain-related fear-avoidance in youth that has demonstrated good indices of reliability and validity, treatment responsiveness, and associations with brain circuitry alterations. This study describes the development and psychometric examination of the FOPQC-SF, a short form of the original measure. ⋯ The 3-month test-retest reliability estimates (N = 94) were strong, and there was preliminary evidence of responsivity to change. To aid integration into intervention trials and clinical practice, we provide clinical reference points and a criterion to assess reliable change. The short form could be used for rapid identification of pain-related fear and avoidance in youth during clinic evaluations, and is optimized for clinical registries.
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Approximately 1.7 million youth suffer from debilitating chronic pain in the US alone, conferring risk of continued pain in adulthood. Aberrations in threat-safety (T-S) discrimination are proposed to contribute to pain chronicity in adults and youth by interacting with pain-related distress. Yet, few studies have examined the neural circuitry underlying T-S discrimination in patients with chronic pain or how T-S discrimination relates to pain-related distress. ⋯ In addition, they showed decreased frontal (vmPFC) activation and aberrant frontolimbic connectivity in response to a learned safety cue (CS-). Patients with low pain-related distress and healthy controls appeared strikingly similar across brain and behavior. These findings indicate that altered T-S discrimination, mediated by frontolimbic activation and connectivity, may be one mechanism maintaining pain chronicity in adolescents with high levels of pain-related distress.
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Preventing and treating opioid dependence and withdrawal is a major clinical challenge, and the underlying mechanisms of opioid dependence and withdrawal remain elusive. We hypothesized that prolonged morphine exposure or chronic inflammation-induced μ-opioid receptor activity serves as a severe stress that elicits neuronal alterations and recapitulates events during development. Here, we report that Wnt signaling, which is important in developmental processes of the nervous system, plays a critical role in withdrawal symptoms from opioid receptor activation in mice. ⋯ In the DH, Wnt5b, acts through the atypical Wnt-Ryk receptor and alternative Wnt-YAP/TAZ signaling pathways, contributing to the naloxone-precipitated opioid withdrawal-like behavioral symptoms and hyperalgesia. Inhibition of Wnt synthesis and blockage of Wnt signaling pathways greatly suppress the behavioral and neurochemical alterations after naloxone-precipitated withdrawal. These findings reveal a critical mechanism underlying naloxone-precipitated opioid withdrawal, suggesting that targeting Wnt5b synthesis in DRG neurons and Wnt signaling in DH may be an effective approach for prevention and treatment of opioid withdrawal syndromes, as well as the transition from acute to chronic pain.
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Complex regional pain syndrome (CRPS) develops after-limb injury, with persistent pain and deficits in movement frequently co-occurring. The striatum is critical for mediating multiple mechanisms that are often aberrant in CRPS, which includes sensory and pain processing, motor function, and goal-directed behaviors associated with movement. Yet, much remains unknown with regards to the morphological and functional properties of the striatum and its subregions in this disease. ⋯ These clinical pain- and movement-related findings in CRPS patients were concomitant with bilateral decreases in gray matter density in the putamen as well as functional connectivity increases and decreases among the putamen and pre-/postcentral gyri and cerebellum, respectively. Importantly, higher levels of clinical pain and motor impairment were associated with increased putamen-pre-/postcentral gyri functional connectivity strengths. Collectively, these findings suggest that putaminal alterations, specifically the functional interactions with sensorimotor structures, may underpin clinical pain and motor impairment in chronic CRPS patients.