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Introduction: Effective treatment for Complex Regional Pain Syndrome (CRPS), a chronic pain condition, is challenging. Cognitive Multisensory Rehabilitation (CMR) is a cognitive and sensorimotor treatment approach aimed at restoring function that targets cognitive, somatosensory, and multisensory functions through sensory discrimination tasks., Purpose: We aimed to apply CMR to treat CRPS within our clinical practice. Clinically, we have found promising results in reducing pain and other common features of CRPS, such as Body Perception Disturbances (BPD)., Methods: In this clinical case series, four CRPS patients who participated in a two-week interdisciplinary CRPS rehabilitation program at the National Complex Regional Pain Syndrome Service in Bath, UK received CMR as part of their treatment. A combination of self-reported measures and clinical outcomes were collected pre and post-rehabilitation program., Results: Functional improvements and a reduction on BPD were observed in all clinical cases., Discussion: We demonstrate how CMR may improve several CRPS-related features that often hinder rehabilitation in people living with CRPS., Conclusion: Research involving larger cohorts are necessary to provide empirical evidence of the application of CMR in treating CRPS.

There is currently an emphasis on the biopsychosocial concept of pain in pain therapy programs. However, the complexity of chronic pain, in particular its importance for those affected by it, can only be insufficiently captured with this concept. This is due to the fact that, to date, one core aspect of the phenomenon chronic pain has only rarely been taken into account: its existential character. Chronic pain can threaten the self-image and the individual's understanding of the world, their wishes and goals in life, and ultimately the entire integrity of those affected. Statements by chronic pain sufferers show that such pain always represents an existential experience and affects the person as a whole. Two aspects make this very clear: the existential despair of the pain on the one hand, as well as questions of meaning and reorientation on the other. Current treatment concepts, however, do not adequately consider the existential character of such challenges. Chronic pain should therefore always be perceived and treated from a holistic perspective. In this context, the aspects of recognizing its uniqueness, helping to express the pain and giving space to the experience are to be given special consideration in order to support chronic pain patients in dealing with their pain., (© 2022. The Author(s).)

This work aimed to test the effect of 7-day exposure of rats to multifunctional enkephalin analogs LYS739 and LYS744 at doses of 3 mg/kg and 10 mg/kg on the protein composition of rat spleen lymphocytes, brain cortex, and hippocampus. Alterations of proteome induced by LYS739 and LYS744 were compared with those elicited by morphine. The changes in rat proteome profiles were analyzed by label-free quantification (MaxLFQ). Proteomic analysis indicated that the treatment with 3 mg/kg of LYS744 caused significant alterations in protein expression levels in spleen lymphocytes (45), rat brain cortex (31), and hippocampus (42). The identified proteins were primarily involved in RNA processing and the regulation of cytoskeletal dynamics. In spleen lymphocytes, the administration of the higher 10 mg/kg dose of both enkephalin analogs caused major, extensive modifications in protein expression levels: LYS739 (119) and LYS744 (182). Among these changes, the number of proteins associated with immune responses and apoptotic processes was increased. LYS739 treatment resulted in the highest number of alterations in the rat brain cortex (152) and hippocampus (45). The altered proteins were functionally related to the regulation of transcription and cytoskeletal reorganization, which plays an essential role in neuronal plasticity. Administration with LYS744 did not increase the number of altered proteins in the brain cortex (26) and hippocampus (26). Our findings demonstrate that the effect of κ-OR full antagonism of LYS744 is opposite in the central nervous system and the peripheral region (spleen lymphocytes).

Chronic pain is known as ongoing pain that lasts longer than three months with increasing healing time. It is approximated that 20% of adults of different sexes, races, and socioeconomic backgrounds fall victim to chronic pain. It is a result of several factors and can have lifelong effects. Pain is a complex matter to measure; therefore, the physician needs to understand the patient's health state to create a management plan tending to each issue adequately. There are many complications of such pain, and it can interfere terribly with an individual's quality of life. This article has reviewed the complex pathogenesis of chronic pain and the spectrum of non-pharmacologic modalities and pharmacological treatment options. It has also explored the efficacy of certain drugs and underlined the importance of nonpharmacological options such as physical exercise, cognitive therapy, and physical modalities to treat chronic pain and all the conditions that accompany this disorder., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Kela et al.)

Purpose of Review: Radiofrequency ablation (RFA) has become an increasingly widespread treatment tool for various chronic pain syndromes within the last two decades with the majority of publications on the topic coming after 2006. Not only are clinicians using RFA to treat more peripheral nerve pain syndromes but the technology itself is evolving quickly to the point that it is nearly impossible to stay abreast on the complexity of such a diversely utilized instrument. This review summarizes studies that focus on the use of RFA for peripheral nerve neurotomy and anatomical studies regarding RFA published between 2015 and 2020., Recent Findings: Topics in this review include anatomical regions or nerves of the body published since 2015. Significant findings are summarized in each section. Peripheral nerve RFA is rapidly changing. Many studies have been performed over the last 5 years showing the usefulness of RFA., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: To compare the effectiveness of three techniques of collagen injection in the treatment of low back pain (LBP) in lumbar spondylosis., Material and Methods: In this randomized prospective study, 30 patients with lumbar spondylosis were assigned to 3 groups: subcutaneous (Group A, n = 10), periradicular (Group B, n = 10) and epidural (Group C, n = 10). Collagen injections were administered once a week (4 injections in total). Assessment involved a visual pain scale (VAS) (0-10), Oswestry scale (0-50), Laitinen scale (0-16) and One Leg Stance Test (OLST) - time to onset of pain in the support limb. Patients were assessed at the start of treatment (W0), on completion of treatment (W1) and 1 month after completion of treatment (W2)., Results: Improvement was seen with all three techniques of collagen administration. The minimal clinically important difference (MID) of 3 points on the VAS scale was noted in 44% of patients in Group A, 40% of patients in Group B and 60% of Group C. The MID for the Oswestry scale, determined at 10 points, was achieved in 56%, 50% and 20% of patients, respectively, while the MID for the Laitinen scale, determined at 4 points, was achieved in 56%, 30% and 40% of patients, respectively. All treated patients achieved the reference value of 30 seconds for OLST only in Group A., Conclusion: Subcutaneous administration of collagen is not inferior in terms of effectiveness to periradicular and epidural injections in the treatment of LBP in lumbar spondylosis.

Background: Chronic pain is one of the most common complaints of cancer patients. There are many pharmacological and non-pharmacological treatment modalities used for the treatment of pain. Nonetheless, non-pharmacological interventions are preferred because of potential side effects in cases resistant to medical therapy that require a dose increase or potent drug use. In most real-life situations, the decision on which technique to choose is based on the clinical but subjective decisions of the practitioners. This study aimed to find out the best non-pharmacological treatment option for patients with chronic cancer pain by following a rational and reasonable approach., Methods: Since the evaluation of treatment options requires to make a comparison between a number of alternatives in the light of certain criteria, we utilize the order relation analysis (G1-method) which is a method for determining the weights based on the improved Analytic Hierarchy Process (AHP). The method uses the relative importances on prioritizing the four criteria and eight sub-criteria defined by the experts of three pain physicians, one oncologist, and one oncologic surgeon. Four alternatives are then compared according to the Technique for Order Preference by Similarity to Ideal Solution (TOPSIS) using the verbal subjective judgments of the practitioners., Results: Obtained results indicate that the general medical condition of the patient and the stage of the cancer are the essential factors in the selection of the treatment method. It is followed by the extent of the pain and the level of evidence, respectively. According to the evaluations performed, spinal port and splanchnic nerve radiofrequency thermocoagulation treatments are the first and second priority methods for pain treatment, respectively, compared to lumbar epidural catheter and celiac plexus block., Conclusions: The results of this study emphasize the need to integrate critical criteria into the decision-making process objectively. This is the first study in which multi-criteria decision-making tools are used in the evaluation and selection of pain management methods in cancer patients.

Adenylyl cyclases type 1 (AC1) and 8 (AC8) are group 1 transmembrane adenylyl cyclases (AC) that are stimulated by Ca 2+ /calmodulin. Studies have shown that mice depleted of AC1 have attenuated inflammatory pain response, while AC1/AC8 double-knockout mice display both attenuated pain response and opioid dependence. Thus, AC1 has emerged as a promising new target for treating chronic pain and opioid abuse. We discovered that the 1,3,4-oxadiazole scaffold inhibits Ca 2+ /calmodulin-stimulated cyclic adenosine 3',5'-monophosphate (cAMP) production in cells stably expressing either AC1 or AC8. We then carried out structure-activity relationship studies, in which we designed and synthesized 65 analogs, to modulate potency and selectivity versus each AC isoform in cells. Furthermore, molecular docking of the analogs into an AC1 homology model suggests the molecules may bind at the ATP binding site. Finally, a prioritized analog was tested in a mouse model of inflammatory pain and exhibited modest analgesic properties. In summary, our data indicate the 1,3,4-oxadiazoles represent a novel scaffold for the cellular inhibition of Ca 2+ /calmodulin-stimulated AC1- and AC8 cAMP and warrant further exploration as potential lead compounds for the treatment of chronic inflammatory pain., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Pain catastrophizing and pain acceptance have been shown to be associated with improvements after participation in cognitive behaviorally-based treatment (CBT) for chronic pain. However, it is not yet clear how important each of these factors is relative to the other. Furthermore, it is also not clear if multidisciplinary pain treatment has the same impact on the two primary dimensions of pain acceptance (activity engagement and pain willingness), and whether their role in explaining treatment outcome differs as a function of the outcomes under study. The aim of this study was to examine the relative importance of changes in pain catastrophizing, activity engagement and pain willingness as predictors of the benefits of a multidisciplinary CBT for chronic pain. 186 adults with chronic pain participated. Pain catastrophizing and activity engagement, but not pain willingness, were significantly associated with treatment outcome. Moreover, each one evidenced different patterns of associations with outcomes. Specifically, while changes in both were associated with improvements in depressive symptoms, only catastrophizing was associated with improvements in pain intensity and only activity engagement was associated with improvements in pain-related disability.

Unlabelled: Neuroplastic changes in brain structure and function are not only a consequence of chronic pain but are involved in the maintenance of pain symptoms. Thus, promotion of adaptive, treatment-responsive neuroplasticity represents a promising clinical target. Emerging evidence about the human brain's response to an array of behavioral and environmental interventions may assist in identifying targets to facilitate increased neurobiological receptivity, promoting healthy neuroplastic changes. Specifically, strategies to maximize neuroplastic responsiveness to chronic pain treatment could enhance treatment gains by optimization of learning and positive central nervous system adaptation. Periods of heightened plasticity have been traditionally identified with the early years of development. More recent research, however, has identified a wide spectrum of methods that can be used to "reopen" and enhance plasticity and learning in adults. In addition to transcranial direct current stimulation and transcranial magnetic stimulation, behavioral and pharmacological interventions have been investigated. Intermittent fasting and glucose administration are two propitious strategies, that are noninvasive, inexpensive to administer, implementable in numerous settings, and might be applicable across differing chronic pain treatments. Key findings and neurophysiological mechanisms are summarized, and evidence for the potential clinical contributions of these two strategies toward ameliorating chronic pain is presented., Perspective: Neuroplastic changes are a defining feature of chronic pain and a complicating factor in treatment. Noninvasive strategies to optimize the brain's response to treatment interventions might improve learning and memory, increase the positive adaptability of the central nervous system, and enhance treatment outcomes., (Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.)

Most patients with chronic pain receive multimodal treatment. There is scant literature to guide us, but when approaching combination pharmacotherapy, the practitioner and patient must weigh the benefits with the side effects; many medications have modest effect yet carry significant side effects that can be additive. Chronic pain often leads to depression, anxiety, and deconditioning, which are targets for treatment. Structured interdisciplinary programs are beneficial but costly. Interventions have their place in the treatment of chronic pain and should be a part of a multidisciplinary treatment plan. Further research is needed to validate many common combination treatments., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Pain control in chronic pancreatitis is a major challenge; the mechanisms behind analgesic treatment are poorly understood. This study aims to investigate the differences in pain sensitivity and modulation in chronic pancreatitis patients, based on their clinical response (responders vs nonresponders) to placebo or pregabalin treatment., Methods: This study was part of a randomized, double-blind, placebo-controlled trial evaluating the analgesic effects of pregabalin and placebo in chronic pancreatitis. Post hoc, patients were assigned to one of four groups, ie, responders and nonresponders to pregabalin (n=16; n=15) or placebo (n=12; n=17) treatment. Responders were defined as patients with >30% pain reduction after 3 weeks of treatment. We measured change in pain sensitivity before and after the treatment using electric pain detection thresholds (ePDT) in dermatomes C5 (generalized effects) and Ventral T10 (segmental effects). Descending endogenous pain modulation was quantified via conditioned pain modulation (CPM) paradigm., Results: Sixty patients were analyzed in a per-protocol analysis. ePDT change in C5 was significant vs baseline and greater in pregabalin (1.3 mA) vs placebo responders (-0.1 mA; P=0.015). This was not so for ePDT in Ventral T10. CPM increased more in pregabalin (9%) vs placebo responders (-17%; P<0.001). CPM changed significantly vs baseline only for pregabalin responders (P=0.006)., Conclusion: This hypothesis-generating study provides the first evidence that pain relief with pregabalin is associated with anti-hyperalgesic effects and increased endogenous inhibitory modulation. No such effects were observed in patients experiencing pain relief with the placebo treatment. The mechanisms underlying analgesic response to placebo vs drug treatments are different and, together with their interactions, deserve further study.

Unlabelled: Standardized measures of efficacy are needed to compare analgesic efficacy across trials. The number needed to treat (NNT) is considered a statistically robust and readily interpretable measure to rank the efficacy of treatments, including analgesics. The NNT has become widely utilized to compare the efficacy of chronic pain treatments, helping physicians make treatment decisions and informing decisions for market access, reimbursement, and treatment guidelines. However, the NNT is associated with specific weaknesses in calculation and interpretation not associated with other methods for integrating trial data. These weaknesses include distortions in calculation as placebo effects approach treatment effects, with the possibility of infinite values; difficulties in estimating the NNT's confidence interval; and difficulties in interpretation. The NNT also requires selecting cutoffs of the original variable for dichotomization, with the NNT often changing depending on the cutoff. The NNT also suffers from problems common to other placebo-adjusted endpoints, including being sensitive to study-related and external factors (eg, year of publication). Therefore, clinicians and other stakeholders need to be aware of these issues to correctly calculate, use, and interpret the NNT. Nevertheless, efficacy, as measured by any variable, is only one aspect of a treatment to be considered in determining its place in therapy., Perspective: The NNT has become widely utilized to compare the efficacy of chronic pain treatments. This article reviews the uses of the NNT and the potential problems associated with its calculation, use, and interpretation. Clinicians should be aware of these issues when interpreting clinical trial data based on the NNT., (Copyright © 2015 American Pain Society. Published by Elsevier Inc. All rights reserved.)