Complex regional pain syndrome (CRPS) is a chronic condition that involves significant hyperalgesia of the affected limb, typically accompanied by localized autonomic abnormalities, and frequently motor dysfunction. Although central brain systems are thought to play a role in the development and maintenance of CRPS, these systems have not been well characterized. In this study, we used structural magnetic resonance imaging (sMRI) to characterize differences in gray matter volume between patients with right upper extremity CRPS and matched controls . Analyses were carried out using a whole brain voxel-based morphometry (VBM) approach. The CRPS group showed decreased gray matter volume in several pain-affect regions, including the dorsal insula, left orbitofrontal cortex, and several aspects of the cingulate cortex. Greater gray matter volume in CRPS patients was seen in the bilateral dorsal putamen and right hypothalamus. Correlation analyses with self-reported pain were then performed on the CRPS group. Pain duration was associated with decreased gray matter in the left dorsolateral prefrontal cortex. Pain intensity was positively correlated with volume in the left posterior hippocampus and left amygdala, and negatively correlated with the bilateral dorsolateral prefrontal cortex. Our findings demonstrate that CRPS is associated with abnormal brain system morphology, particularly pain-related sensory, affect, motor, and autonomic systems.

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Objective Chronic overlapping pain conditions (COPCs) represent a co‐aggregation of widespread pain disorders. We characterized differences in physical and psychosocial functioning in patients with chronic migraine (CM) and those with CM and COPCs. Background Patients with CM and COPCs have been identified as a distinct subgroup of patients with CM, and these patients may be vulnerable to greater symptom severity and burden. Methods Data were extracted from Collaborative Health Outcomes Information Registry (an open‐source learning health‐care system), completed at the patients' first visit at a large tertiary care pain management center and electronic medical records. In 1601 patients with CM, the number of non‐cephalic areas of pain endorsed on a body map was used to examine the differences in pain, physical and psychosocial function, adverse life experience, and health‐care utilization. Results Patients endorsing more body map regions reported significantly worse symptoms and function across all domains. Scored on a t‐score metric (mean = 50, SD = 10), endorsement of one additional body map region corresponded with a 0.69‐point increase in pain interference (95% CI = 0.55, 0.82; p < 0.001; Cohen's f = 0.328), 1.15‐point increase in fatigue (95% CI = 0.97, 1.32; p < 0.001; Cohen's f = 0.432), and 1.21‐point decrease in physical function (95% CI = −1.39, −1.03; p < 0.001; Cohen's f = 0.560). Patients with more widespread pain reported approximately 5% more physician visits (95% CI = 0.03, 0.07; p < 0.001), and patients reporting adverse life events prior to age 17 endorsed 22% more body map regions (95% CI = 0.11, 0.32; p < 0.001). Conclusions Patients with CM and other overlapping pain conditions as noted on the body map report significantly worse pain‐related physical function, psychosocial functioning, increased health‐care utilization, and greater association with adverse life experiences, compared with those with localized CM. This study provides further evidence that patients with CM and co‐occurring pain conditions are a distinct subgroup of CM and can be easily identified through patient‐reported outcome measures.

The tumor-suppressor protein p53 belongs to a small gene family that includes p63 and p73. While p53 and p73 regulate cell cycle progression and apoptosis, the major role of p63 appears to be in promoting ectodermal proliferation and differentiation. In this report we describe the cloning of a Xenopus orthologue of mammalian p63 that is extraordinarily conserved in sequence. The major sites of expression of Xenopus p63 mRNA are the epidermis and some neural crest and crest derivatives such as the branchial arches and tail fin. Expression is also observed in the neural plate and in the stomodeal-hypophyseal anlage. Antibodies against p63 detect a nuclear protein that is distributed in a manner similar to that of Xp63 mRNA. Both mRNA and protein are conspicuously absent from regions of the epidermal sensorial layer that are induced to form a number of (but not all) ectodermal placodes and Xp63 protein levels are particularly dynamic in the epidermis of the eye as the lens forms.

BackgroundThe past two decades have witnessed a surge in the use of cervical spine joint procedures including joint injections, nerve blocks and radiofrequency ablation to treat chronic neck pain, yet many aspects of the procedures remain controversial.MethodsIn August 2020, the American Society of Regional Anesthesia and Pain Medicine and the American Academy of Pain Medicine approved and charged the Cervical Joint Working Group to develop neck pain guidelines. Eighteen stakeholder societies were identified, and formal request-for-participation and member nomination letters were sent to those organizations. Participating entities selected panel members and an ad hoc steering committee selected preliminary questions, which were then revised by the full committee. Each question was assigned to a module composed of 4–5 members, who worked with the Subcommittee Lead and the Committee Chairs on preliminary versions, which were sent to the full committee after revisions. We used a modified Delphi method whereby the questions were sent to the committee en bloc and comments were returned in a non-blinded fashion to the Chairs, who incorporated the comments and sent out revised versions until consensus was reached. Before commencing, it was agreed that a recommendation would be noted with >50% agreement among committee members, but a consensus recommendation would require ≥75% agreement.ResultsTwenty questions were selected, with 100% consensus achieved in committee on 17 topics. Among participating organizations, 14 of 15 that voted approved or supported the guidelines en bloc, with 14 questions being approved with no dissensions or abstentions. Specific questions addressed included the value of clinical presentation and imaging in selecting patients for procedures, whether conservative treatment should be used before injections, whether imaging is necessary for blocks, diagnostic and prognostic value of medial branch blocks and intra-articular joint injections, the effects of sedation and injectate volume on validity, whether facet blocks have therapeutic value, what the ideal cut-off value is for designating a block as positive, how many blocks should be performed before radiofrequency ablation, the orientation of electrodes, whether larger lesions translate into higher success rates, whether stimulation should be used before radiofrequency ablation, how best to mitigate complication risks, if different standards should be applied to clinical practice and trials, and the indications for repeating radiofrequency ablation.ConclusionsCervical medial branch radiofrequency ablation may provide benefit to well-selected individuals, with medial branch blocks being more predictive than intra-articular injections. More stringent selection criteria are likely to improve denervation outcomes, but at the expense of false-negatives (ie, lower overall success rate). Clinical trials should be tailored based on objectives, and selection criteria for some may be more stringent than what is ideal in clinical practice.