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.

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.

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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.

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.

Objective To develop and internally validate a multivariable predictive model for days with new‐onset migraine headaches based on patient self‐prediction and exposure to common trigger factors. Background Accurate real‐time forecasting of one’s daily risk of migraine attack could help episodic migraine patients to target preventive medications for susceptible time periods and help decrease the burden of disease. Little is known about the predictive utility of common migraine trigger factors. Methods We recruited adults with episodic migraine through online forums to participate in a 90‐day prospective daily‐diary cohort study conducted through a custom research application for iPhone. Every evening, participants answered questions about migraine occurrence and potential predictors including stress, sleep, caffeine and alcohol consumption, menstruation, and self‐prediction. We developed and estimated multivariable multilevel logistic regression models for the risk of a new‐onset migraine day vs a healthy day and internally validated the models using repeated cross‐validation. Results We had 178 participants complete the study and qualify for the primary analysis which included 1870 migraine events. We found that a decrease in caffeine consumption, higher self‐predicted probability of headache, a higher level of stress, and times within 2 days of the onset of menstruation were positively associated with next‐day migraine risk. The multivariable model predicted migraine risk only slightly better than chance (within‐person C‐statistic: 0.56, 95% CI: 0.54, 0.58). Conclusions In this study, episodic migraine attacks were not predictable based on self‐prediction or on self‐reported exposure to common trigger factors. Improvements in accuracy and breadth of data collection are needed to build clinically useful migraine prediction models.

Background The 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. Methods In 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. Results Twenty 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. Conclusions Cervical 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 b...

Objective To systematically evaluate the efficacy and effectiveness of percutaneous interventional treatments for prevention of migraine through a qualitative and (when possible) quantitative analysis. Methods An expert panel was asked to develop recommendations for the multidisciplinary preventive treatment of migraine, including interventional strategies. The committee conducted a systematic review and (when evidence was sufficient) a meta-analytic review using GRADE criteria and the modified Cochrane risk of bias analysis available in the Covidence data management program. Clinical questions addressed adults with migraine who should be offered prevention. Examined outcomes included headache days, acute medication use, and functional impairment. Acute management of migraine was outside the scope of this guideline. Results The committee screened 1195 studies and assessed 352 by full text, yielding 16 randomized controlled trials that met inclusion criteria. Recommendations/Conclusions As informed by evidence related to the preselected outcomes, adverse event profile, cost, and values and preferences of patients, onabotulinumtoxinA received a strong recommendation for chronic migraine prevention and a weak recommendation against use for episodic migraine prevention. Greater occipital nerve blocks received a weak recommendation for chronic migraine prevention. For greater occipital nerve block, steroid received a weak recommendation against use vs local anesthetic alone. Occipital nerve with supraorbital nerve blocks, sphenopalatine ganglion blocks, cervical spine percutaneous interventions, and implantable stimulation all received weak recommendations for chronic migraine prevention. The committee found insufficient evidence to assess trigger point injections in migraine prevention and highly discouraged use of intrathecal medication.