Neurobiology Of Pain Research Articles

When thinking about pain contributes to suffering: the example of pain catastrophizing.

The extensive literature on the potent role negative thoughts about pain have on the experience of pain and pain-related suffering has documented associations with important neurobiological processes involved in amplifying nociceptive signals. We focus this review on pain catastrophizing (pCAT)- appraisals of pain as threatening, overwhelming, and unmanageable- and review the evidence that these thoughts are learned in childhood through experience and observation of others, particularly caretakers and parents. For children who have learned pCAT, repeated exposures to pain over time activate pCAT and likely contribute to further amplification of pain through changes in the neurobiological pain regulatory systems, which overlap with those regulating the stress response. We propose that repeated pain and stress exposures throughout childhood, adolescence, and into adulthood alter the neurobiology of pain via a repetitive positive feedback loop that increases risk for heightened pain sensitivity over time with repeated exposures. At some point, often precipitated by an acute episode of pain and possibly influenced by allostatic load, pCAT contributes to persistence of episodic or acute pain and exacerbates pain-related suffering. This developmental trajectory is not inevitable, as the impact of pCAT on pain and pain-related suffering can be influenced by various factors. We also present future directions for work in this area.

Pain Neuroscience Education and Neuroimaging-A Narrative Review.

Musculoskeletal pain is a leading cause of medical visits, posing significant challenges both socially and economically, encouraging the scientific community to continue researching and exploring the most effective methods to address the problem. An alternative way to deal with chronic pain is pain neuroscience education (PNE), a lesson plan that addresses the neurobiology, neurophysiology, and nervous system processing of pain. This method takes the place of the conventional one, which connected pain to tissue damage or nociception. As a result, patients are taught that pain is often not a reliable measure of the health of the tissues but rather the outcome of the nervous system interpreting the injury in conjunction with additional psychosocial variables. In addition to finding research that examine, using neuroimaging, whether the administration of PNE has detectable effects at the level of the central nervous system, this narrative review seeks to clarify what PNE is, how it is administered, and if it is an effective treatment for musculoskeletal pain. Based on the findings, it appears that PNE is more therapeutically beneficial when combined with therapeutic exercise, when done one-on-one, and during lengthy, frequent sessions. Lastly, even though PNE has no effect on the morphological properties of the gray matter, it appears to cause decreased activation of the regions linked to pain.

Correlatos Neurais da Dor, Resiliência e Empatia

Currently, pain is understood as a complex phenomenon infl uenced by biopsychosocial factors, as evidenced by the growing body of research in the “new science of pain.” The neurobiology of pain reveals a complex brain network associated with pain perception, with clear implications for emotional and cognition disorders. Empathy and resilience are crucial behavioral skills observed in both humans and animals, with neurobiological bases related to understanding others’ emotions and adapting to adverse situations. However, the association between neural processes related to resilience and empathy with pain pathways still needs to be clarifi ed. To this end, a systematic review was conducted in two databases (PubMed and Lilacs), including English articles without date limitations to achieve broader coverage. Initially, 3,649 studies were identifi ed, and after inclusion and exclusion criteria were applied, 72 relevant articles exploring this interrelation were identifi ed, highlighting neurobiological convergences in pain modulation by empathy and resilience. Empathy activates brain areas linked to understanding others’ emotions, while resilience is associated with adapting to stressful situations, both sharing neurobiological convergences in pain processing. Therapeutic interventions such as mindfulness and psychotherapy show promise in promoting empathy and resilience, off ering new perspectives for chronic pain management. These fi ndings underscore the importance of a multidimensional approach in chronic pain treatment, integrating biopsychosocial considerations to enhance patient outcomes.Keywords: Empathy, resilience, pain, neural pathways

Does pain hurt more in Spanish? The neurobiology of pain among Spanish-English bilingual adults.

We previously found Spanish-English bilingual adults reported higher pain intensity when exposed to painful heat in the language of their stronger cultural orientation. Here, we elucidate brain systems involved in language-driven alterations in pain responses. During separate English- and Spanish-speaking fMRI scanning runs, 39 (21 female) bilingual adults rated painful heat intermixed between culturally evocative images and completed sentence reading tasks. Surveys of cultural identity and language use measured relative preference for US-American vs Hispanic culture (cultural orientation). Participants produced higher intensity ratings in Spanish compared to English. Group-level whole-brain differences in pain-evoked activity between languages emerged in somatosensory, cingulate, precuneus and cerebellar cortex. Regions of interest associated with semantic, attention and somatosensory processing showed higher average pain-evoked responses in participants' culturally preferred language, as did expression of a multivariate pain-predictive pattern. Follow-up moderated mediation analyses showed somatosensory activity mediated language effects on pain intensity, particularly for Hispanic oriented participants. These findings relate to distinct ('meddler', 'spotlight' and 'inducer') hypotheses about the nature of language effects on perception and cognition. Knowledge of language influences on pain could improve efficacy of culturally sensitive treatment approaches across the diversity of Hispanic adults to mitigate documented health disparities in this population.

Calcitonin Gene-Related Peptide-Mediated Trigeminal Ganglionitis: The Biomolecular Link between Temporomandibular Disorders and Chronic Headaches.

A bidirectional causal relationship has been established between temporomandibular disorders (TMDs) and chronic headaches. Recent advances in the neurobiology of chronic pain offer a framework for understanding the comorbidity between these two conditions that might reside in the shared biomolecular mechanisms of peripheral and central sensitization. The initiation of these processes is inflammatory in nature and is most likely mediated by key molecules, including calcitonin gene-related peptide (CGRP). This scoping review proposes that CGRP-mediated neuroinflammation in the trigeminal ganglion may partly explain the biomolecular bidirectional link between TMDs and chronic headaches. Finally, clinical implications of this neuropathologic process are briefly discussed.

Slaughtering of Water Buffalo (Bubalus bubalis) with and without Stunning: A Focus on the Neurobiology of Pain, Hyperalgesia, and Sensitization.

The slaughter process in livestock is considered a stressor where the transport and handling of animals, as well as the selected stunning and bleeding methods, can cause acute pain, distress, and suffering. In water buffaloes, although stunning is known to be performed before bleeding to induce unconsciousness, no emphasis is made on the nociceptive events during this process. Particularly, current mechanical stunning methods applied to cattle are unsuitable for water buffaloes due to anatomical differences in the skull from other large ruminants. Furthermore, although very high-pressure pneumatic (200-220 psi) may be effective in the frontal position for lighter-weight water buffalos, for heavier animals, it is less likely to be effective. The present review aims: (1) to analyze the anatomical particularities of water buffaloes to discuss the importance of selecting a stunning method suitable for buffaloes, and (2) to revise the potential pain-related consequences, such as hyperalgesia and sensitization, and the signs to assess the stun quality and death to comprehend the relevance of a proper technique according to the species.

Neurobiology and long-term impact of bladder-filling pain in humans: a Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) research network study.

Pain with bladder filling remains an unexplained clinical presentation with limited treatment options. Here, we aim to establish the clinical significance of bladder filling pain using a standardized test and the associated neural signature. We studied individuals diagnosed with urologic chronic pelvic pain syndrome (UCPPS) recruited as part of the multidisciplinary approach to the study of chronic pelvic pain (MAPP) study. Patients with urologic chronic pelvic pain syndrome (N = 429) and pain-free controls (N = 72) underwent a test in which they consumed 350 mL of water and then reported pain across an hour-long period at baseline and 6 months. We used latent class trajectory models of these pain ratings to define UCPPS subtypes at both baseline and 6 months. Magnetic resonance imaging of the brain postconsumption was used to examine neurobiologic differences between the subtypes. Healthcare utilization and symptom flare-ups were assessed over the following 18 months. Two distinct UCPPS subtypes were identified, one showing substantial pain related to bladder filling and another with little to no pain throughout the test. These distinct subtypes were seen at both baseline and 6 month timepoints. The UCPPS subtype with bladder-filling pain (BFP+) had altered morphology and increased functional activity in brain areas involved in sensory and pain processing. Bladder-filling pain positive status predicted increased symptom flare-ups and healthcare utilization over the subsequent 18 months when controlling for symptom severity and a self-reported history of bladder-filling pain. These results both highlight the importance of assessing bladder filling pain in heterogeneous populations and demonstrate that persistent bladder-filling pain profoundly affects the brain.

The introduction and current status of the multidimensional model of pain neurobiology.

Conceptual models are useful because they guide our practical actions related to whatever is represented by the model; this includes research that reveals the limitations of these actions and the potential for their improvement. These statements apply to many aspects of daily life and especially to pain as a challenge for both clinical practice specifically and neurobiology generally. In the first half of the 20th century, our conceptual model of pain, to the extent that it existed at all, was based on evidence supporting the proposition that pain emerged from activity within a very spatially limited set of central nervous system (CNS) structures located within the cerebral cortex and it's oligosynaptic connections with the thalamus. This CNS activity was strongly associated with the activation of physiologically distinct and specialized somatovisceral afferent fibers. All, or nearly all, aspects of the pain experience were thought to arise from, and be modified by, changes in that localized CNS activity. There was no compelling and widely accepted reason to consider an alternative model. However, neurophysiological, neuroanatomical, behavioral, and clinical evidence emerging in the late mid-20th century prompted a reconsideration of the prevailing model of pain neurobiology. Based on this new evidence and the perceived limitations of the prevailing model, pain could then be reasonably conceived as a multidimensional experience arising from the conjoint activation of physiologically and anatomically distinct but interacting CNS structures each separately mediating sensory discriminative, affective, and cognitive aspects of pain. This brief historical review describes the intellectual climate at the time this multidimensional model was proposed, the dispositions for resisting or accepting it, and concludes with a comment on the current status of the model as a fusion of distributed activations that create a unified perception of pain.

Pain specialist management of sexual pain—I: foundations

Abstract Introduction The biopsychosocial model of care for women with sexual pain is a widely endorsed approach melding the expertise of multiple professional disciplines. Interventional pain management provides specialized diagnosis and treatment of chronic pain as part of the interdisciplinary care team. Diagnosis and treatment strategies are built on the foundational knowledge of the causes of female sexual pain, appreciation of the intrapersonal, interpersonal, and sociocultural contexts which shape pain, and the psychological and neurophysiological effect of chronic pain. This first paper in a series of four lays the groundwork for applying the perspectives, approaches, and therapeutic treatment options inherent in the specialty of pain management. Objectives To provide a current summary of the neurobiology, intrapersonal and interpersonal aspects of female sexual pain within a chronic pain paradigm. Describe the role of an interventional pain specialist as part of an interdisciplinary sexual pain team. Methods Internet search engines, PubMed and Cochrane Library were searched for relevant articles on female sexual pain within the scope of practice of pain management. Results A thorough review of the literature was conducted to include basic science studies, clinical trials, systematic reviews, consensus statements, and case-reports. The neurobiological and psychological aspects of sexual pain were described within a chronic pain paradigm. The perspective of a pain specialist on female sexual pain was presented. Conclusion The care of women with sexual pain is highly complex and must be individualized based on the characteristics of the pain, its chronicity, and all the ways the condition impacts each woman. Physiological changes seen in chronic pain are likely to be present in most women with sexual pain. Awareness of the replete biopsychosocial dimensions of sexual pain promotes the goals of interdisciplinary care and provides a foundation for each specialty in the team. The way pain management specialists employ that knowledge for women with sexual pain will be examined in subsequent papers.

The neurobiology of pain and facial movements in rodents: Clinical applications and current research.

One of the most controversial aspects of the use of animals in science is the production of pain. Pain is a central ethical concern. The activation of neural pathways involved in the pain response has physiological, endocrine, and behavioral consequences, that can affect both the health and welfare of the animals, as well as the validity of research. The strategy to prevent these consequences requires understanding of the nociception process, pain itself, and how assessment can be performed using validated, non-invasive methods. The study of facial expressions related to pain has undergone considerable study with the finding that certain movements of the facial muscles (called facial action units) are associated with the presence and intensity of pain. This review, focused on rodents, discusses the neurobiology of facial expressions, clinical applications, and current research designed to better understand pain and the nociceptive pathway as a strategy for implementing refinement in biomedical research.

The Welfare of Fighting Dogs: Wounds, Neurobiology of Pain, Legal Aspects and the Potential Role of the Veterinary Profession.

Simple SummaryDog fights are cruel and harmful events which have a clear impact on animal welfare. For this reason, many countries have banned these events via statute. However, in some regions of the world they are still legal. Moreover, the enforcement of legal bans can be problematic in countries where they are illegal, and they may still occur. This article provides background information on dog fighting and the welfare implications of it. This includes consideration for the pain inflicted, and its mechanisms of perception and recognition. It also analyzes the injuries and emotions experienced by the animals and considers the profile of the breeders and handlers involved in the activity. Since welfare concerns often extend beyond the animals’ fighting lives, a discussion around the possibilities of reintroduction into suitable environments for these animals is also made. Finally, attention is turned to the role that veterinarians can and should play in dealing with these issues of welfare.Throughout history it has been common to practice activities which significantly impact on animal welfare. Animal fighting, including dogfighting, is a prime example where animals often require veterinary care, either to treat wounds and fractures or to manage pain associated with tissue and where death may even result. Amongst the detrimental health effects arising are the sensory alterations that these injuries cause, which not only include acute or chronic pain but can also trigger a greater sensitivity to other harmful (hyperalgesia) or even innocuous stimuli (allodynia). These neurobiological aspects are often ignored and the erroneous assumption made that the breeds engaged in organized fighting have a high pain threshold or, at least, they present reduced or delayed responses to painful stimuli. However, it is now widely recognized that the damage these dogs suffer is not only physical but psychological, emotional, and sensory. Due to the impact fighting has on canine welfare, it is necessary to propose solution strategies, especially educational ones, i.e., educating people and training veterinarians, the latter potentially playing a key role in alerting people to all dog welfare issues. Therefore, the aim of this review is to describe the risk factors associated with dogfighting generally (dog temperament, age, sex, nutrition, testosterone levels, environment, isolation conditions, socialization, education, or training). A neurobiological approach to this topic is taken to discuss the impact on dog pain and emotion. Finally, a general discussion of the format of guidelines and laws that seek to sanction them is presented. The role that veterinarians can play in advancing dog welfare, rehabilitating dogs, and educating the public is also considered.

Pharmacological Strategies for Suicide Prevention Based on the Social Pain Model: A Scoping Review

Suicidal behaviour is a public health problem whose magnitude is both substantial and increasing. Since many individuals seek medical treatment following a suicide attempt, strategies aimed at reducing further attempts in this population are a valid and feasible secondary prevention approach. An evaluation of the available evidence suggests that existing treatment approaches have a limited efficacy in this setting, highlighting the need for innovative approaches to suicide prevention. Existing research on the neurobiology of social pain has highlighted the importance of this phenomenon as a risk factor for suicide, and has also yielded several attractive targets for pharmacological strategies that could reduce suicidality in patients with suicidal ideation or a recent attempt. In this paper, the evidence related to these targets is synthesized and critically evaluated. The way in which social pain is related to the “anti-suicidal” properties of recently approved treatments, such as ketamine and psilocybin, is examined. Such strategies may be effective for the short-term reduction in suicidal ideation and behaviour, particularly in cases where social pain is identified as a contributory factor. These pharmacological approaches may be effective regardless of the presence or absence of a specific psychiatric diagnosis, but they require careful evaluation.

Comparison of Pain-Like behaviors in two surgical incision animal models in C57BL/6J mice

BackgroundManagement of pain post-surgery is crucial for tissue healing in both veterinary and human medicine. Overuse of some analgesics such as opioids may lead to addictions and worsen pain syndromes (opioid-induced hyperalgesia), while underuse of it may affect the welfare of the patient. Therefore, the importance of using surgery models in laboratory animals is increasing, with the goal of improving our understanding of pain neurobiology and developing safer analgesics. MethodsWe compared the widely used plantar incision model with the laparotomy surgery model and measured pain-related behaviors using both spontaneous and evoked responses in female and male C57BL/6J mice. Additionally, we assessed conditioned place preference (CPP) and sucrose preference tests to measure pain-induced motivation for the analgesic ketoprofen and anhedonia-like behavior. ResultsLaparotomized mice showed increased abdominal sensitivity while paw-incised mice showed increased paw thermal and mechanical sensitivity up to seven days post-surgery. Laparotomy surgery reduced all spontaneous behaviors in our study however this effect dissipated by 24 h post-laparotomy. On the other hand, paw incision only reduced the percentage of cage hanging in a sex-dependent manner at 6 h post-incision. We also showed that both surgery models increased conditioned place preference for ketoprofen while preference for sucrose was only reduced at 24 h post-laparotomy. Laporatomy, but not paw incision, induced a decrease in body weight at 24 h post-surgery. Neither surgery model affected fluid intake. ConclusionOur results indicate that post-surgery hypersensitivity and behavioral deficits may differ by the incision site. Furthermore, factors associated with the surgery including length of the incision, duration of the anesthesia, and the layers that received stitches may affect subsequent spontaneous behaviors. These findings may help to improve drug development or the choice of the effective analgesic, depending on the surgery type.

Druggable Targets and Compounds with Both Antinociceptive and Antipruritic Effects.

Pain and itch are both important manifestations of various disorders, such as herpes zoster, atopic dermatitis, and psoriasis. Growing evidence suggests that both sensations have shared mediators, overlapping neural circuitry, and similarities in sensitization processes. In fact, pain and itch coexist in some disorders. Determining pharmaceutical agents and targets for treating pain and itch concurrently is of scientific and clinical relevance. Here we review the neurobiology of pain and itch and discuss the pharmaceutical targets as well as novel compounds effective for the concurrent treatment of these sensations.

Face detection and grimace scale prediction of white furred mice

Studying the facial expressions of humans has been one of the major applications of computer vision. An open question is whether common machine learning techniques can also be used to track behaviors of animals, which is a less explored research problem. Since animals are not capable of verbal communication, computer vision solutions can provide valuable information to track the animal’s state. We are particularly interested in pain neurobiology research, where rodent models are extensively used to investigate pain interventions. A grimace scale is used to understand the suffering of a mouse in the presence of interventions, which is inferred from various facial features such as the shape of the eyes and ears. In this work, we automate the prediction of the grimace scale on white furred mice using a machine learning approach, following the same principles used for human facial expression recognition: face detection, landmark region extraction, and expression recognition. We demonstrate the use of the you only look once (YOLO) framework for face detection of the mice with outstanding results. For eye region extraction and grimace pain prediction, we propose a novel structure based on a dilated convolutional network. The experimental results are promising, showing that it is possible to differentiate among the pain scale of the mice.

Community Fibromyalgia Support Groups: Who do they serve and could they improve outcomes?

Purpose: Fibromyalgia is a chronic pain condition. The National Institute for Health and Care Excellence Chronic Pain Guideline Scope states that “there has been little change in the prevalence and time course of chronic pain despite significant scientific advances to improve understanding of the neurobiology of pain”. In chronic conditions, there is a massive role for self-management. One method to encourage better self-management and self-care are disease-specific community-run support groups. The Salford Fibromyalgia Support Group acts as an informal educational session and a peer-led support network. Most of this groups’ members are former, or current, patients of the nearby Salford Royal Hospitals’ Rheumatology and Physiotherapy departments.

Book Review: The Oxford Handbook of the Neurobiology of Pain by J. N. Wood

Book Review: <i>The Oxford Handbook of the Neurobiology of Pain</i> by J. N. Wood

Book Review: My Bodyguard Brain - How Your Brain Uses Pain to Protect You.

Review of a practical resource providing children with ongoing pain (and their parents) information of the neurobiology of pain. The book 'My Bodyguard Brain - How your brain uses pain to protect you' explains why we feel pain. The brain makes pain when it notices any sort of danger. Pain is associated with acute injury but it can also be evoked by social interaction and unpleasant emotion that children don't know how to deal with. The text and drawings explain in a child-friendly way how your 'Bodyguard' brain wants to look after you, and how it sometimes gets a bit 'too good' at that job. It is a book I would recommend for teachers and clinicians dealing with children experiencing chronic pain. Ongoing pain in children is a huge problem in society. Paediatric pain should matter to everyone. It affects approximately one quarter to one third of all children and adolescents. Children with chronic pain have often cut back all their normal activities like school, sports, social life and sleep. Almost 60% of these children become adults experiencing pain and 50% of the children with pain has a parent suffering from chronic pain. Understanding what you feel will turn the oversensitive alarm down and is the first step to improve the lives of children and adolescents with pain.

Acute and Chronic Pain from Facial Skin and Oral Mucosa: Unique Neurobiology and Challenging Treatment.

The oral cavity is a portal into the digestive system, which exhibits unique sensory properties. Like facial skin, the oral mucosa needs to be exquisitely sensitive and selective, in order to detect harmful toxins versus edible food. Chemosensation and somatosensation by multiple receptors, including transient receptor potential channels, are well-developed to meet these needs. In contrast to facial skin, however, the oral mucosa rarely exhibits itch responses. Like the gut, the oral cavity performs mechanical and chemical digestion. Therefore, the oral mucosa needs to be insensitive, to some degree, in order to endure noxious irritation. Persistent pain from the oral mucosa is often due to ulcers, involving both tissue injury and infection. Trigeminal nerve injury and trigeminal neuralgia produce intractable pain in the orofacial skin and the oral mucosa, through mechanisms distinct from those seen in the spinal area, which is particularly difficult to predict or treat. The diagnosis and treatment of idiopathic chronic pain, such as atypical odontalgia (idiopathic painful trigeminal neuropathy or post-traumatic trigeminal neuropathy) and burning mouth syndrome, remain especially challenging. The central integration of gustatory inputs might modulate chronic oral and facial pain. A lack of pain in chronic inflammation inside the oral cavity, such as chronic periodontitis, involves the specialized functioning of oral bacteria. A more detailed understanding of the unique neurobiology of pain from the orofacial skin and the oral mucosa should help us develop novel methods for better treating persistent orofacial pain.

Comparative safety review of current treatment options for chronic low back pain and unmet needs: a narrative review

ABSTRACT Introduction: The healthcare expenditures in the United States are substantial for the management of refractory, chronic low back pain (CLBP). The objective of this review is to summarize and evaluate the safety profiles of different pharmacological treatment options used in the management of CLBP. Areas covered: The authors conducted a search of randomized controlled trials (RCTs) assessing the safety profiles of different pharmacological agents used in the management of CLBP. This narrative review covered corticosteroids, opioids, antidepressants, gabapentinoids, nonsteroidal anti-inflammatory drugs, muscle relaxants, anti-nerve growth factor antibodies and topical agents, as monotherapy or in combination. Expert opinion: The risk-benefit ratio of a particular treatment is a subject driving the ongoing development of pharmaceuticals. The most commonly reported AEs across all drug classes are of gastrointestinal nature, followed by neurological and skin-related. These AEs include nausea, dizziness, constipation, arthralgia, headache, dry mouth, pruritus, etc. The majority of the AEs reported are not life-threatening, although they may lower patients’ quality of life, thus, affecting their compliance. One of the biggest limitations of our review stems from the paucity of safety assessments in published RCTs. Advances in our understanding of the neurobiology of pain will promote development of new therapeutic strategies.