Neurobiology Of Pain Research Articles

The Promise of Effective Pain Treatment Outcomes: Rallying Academic Centers to Lead the Charge.

### The Pain of the Mind is Worse Than the Pain of the Body #### Publilius Syrus The dramatic impact of chronic pain was captured in a recent European study that followed patients suffering with chronic pain for 1 year: 40% of those patients had more pain and 40% had less pain, but 100% reported major, negative impacts of chronic pain on their quality of life ⇓. Half of patients believed that everything possible had been done to manage their pain. This insight into how patients with chronic pain fare reveals a number of salient points, perhaps most importantly highlighting this condition that persists without cure. Furthermore, accumulating evidence suggests that emotional processing in brain networks is more involved in chronic pain ⇓ alluding to the nature of the associated suffering with the condition. Despite significant advances in pain neurobiology, there remains an urgent need to define outcome measures for treatment options and to understand both short-term (i.e., symptom control) and long-term (i.e., disease modification) approaches to treatments that really work. Unfortunately, pain remains one of the most difficult conditions to live with and to treat. One of the major problems is that because treatments are not highly effective across populations, a wide variety of approaches is frequently used combining various pharmacological, interventional, and behavioral treatments outside of the setting of a coordinated interdisciplinary program. In academic pain clinics, where a more rational approach to treatment may be possible because of hospital standards and relevant lack of financial conflict of interests, financial pressures remain a factor. Patients will continue to reach out in hope that some current or new treatment will be highly effective. Without question, some patients receive treatments that are highly effective such as spinal cord stimulation for chronic radicular leg pain in the setting of postlaminectomy syndrome, but this is generally not defined in a rigorous way as compared to treatment for an …

Early insights into the neurobiology of pain in sickle cell disease: A systematic review of the literature.

Novel insights into the neurobiology of sickle cell disease (SCD) pain have recently been discovered. We systematically reviewed the literature focusing on original research that examined the biology of pain in SCD and/or addressed assessment or treatment of neuropathic pain in SCD. This review of 15 articles that met inclusion criteria provides epidemiological, basic, and clinical data that support central and/or peripheral nervous system abnormalities likely contribute to sickle cell pain. Continued basic and clinical investigation into pain neurobiology is imperative to translate these discoveries into novel ways to assess and treat neuropathic pain and decrease patient suffering.

Chronic multisite pain in major depression and bipolar disorder: cross-sectional study of 149,611 participants in UK Biobank.

BackgroundChronic pain has a strong association with major depressive disorder (MDD), but there is a relative paucity of studies on the association between chronic multisite pain and bipolar disorder (BD). Such studies are required to help elucidate the complex biological and psychological overlap between pain and mood disorders. The aim of this study is to investigate the relationship between chronic multisite pain and mood disorder across the unipolar-bipolar spectrum.MethodsWe conducted a cross-sectional study of 149,611 UK Biobank participants. Self-reported depressive and bipolar features were used to categorise participants into MDD and BD groups and a non-mood disordered comparison group. Multinomial logistic regression was used to establish whether there was an association between extent of chronic pain (independent variable) and mood disorder category (dependent variable), using no pain as the referent category, and adjusting for a wide range of potential sociodemographic, lifestyle and comorbidity confounders.ResultsMultisite pain was significantly more prevalent in participants with BD and MDD, for example, 4–7 pain sites: BD 5.8%, MDD 4.5%, and comparison group 1.8% (p < 0.001). A relationship was observed between extent of chronic pain and risk of BD and persisted after adjusting for confounders (relative to individuals with no chronic pain): 2–3 sites RRR of BD 1.84 (95% CI 1.61, 2.11); 4–7 sites RRR of BD 2.39 (95% CI 1.88, 3.03) and widespread pain RRR of BD 2.37 (95% CI 1.73, 3.23). A similar relationship was observed between chronic pain and MDD: 2–3 sites RRR of MDD 1.59 (95% CI 1.54, 1.65); 4–7 sites RRR of MDD 2.13 (95% CI 1.98, 2.30); widespread pain RRR of MDD 1.86 (95% CI 1.66, 2.08).ConclusionsIndividuals who report chronic pain and multiple sites of pain are more likely to have MDD and are at higher risk of BD. These findings highlight an important aspect of comorbidity in MDD and BD and may have implications for understanding the shared neurobiology of chronic pain and mood disorders.Electronic supplementary materialThe online version of this article (doi:10.1186/s12888-014-0350-4) contains supplementary material, which is available to authorized users.

Pain-novel targets and new technologies.

Pain-novel targets and new technologies.

Adenosine triphosphate drives head and neck cancer pain through P2X2/3 heterotrimers.

IntroductionCancer pain creates a poor quality of life and decreases survival. The basic neurobiology of cancer pain is poorly understood. Adenosine triphosphate (ATP) and the ATP ionotropic receptor subunits, P2X2 and P2X3, mediate cancer pain in animal models; however, it is unknown whether this mechanism operates in human, and if so, what the relative contribution of P2X2- and P2X3-containing trimeric channels to cancer pain is. Here, we studied head and neck squamous cell carcinoma (HNSCC), which causes the highest level of function-induced pain relative to other types of cancer.ResultsWe show that the human HNSCC tissues contain significantly increased levels of ATP compared to the matched normal tissues. The high levels of ATP are secreted by the cancer and positively correlate with self-reported function-induced pain in patients. The human HNSCC microenvironment is densely innervated by nerve fibers expressing both P2X2 and P2X3 subunits. In animal models of HNSCC we showed that ATP in the cancer microenvironment likely heightens pain perception through the P2X2/3 trimeric receptors. Nerve growth factor (NGF), another cancer-derived pain mediator found in both human and mouse HNSCC, induces P2X2 and P2X3 hypersensitivity and increases subunit expression in murine trigeminal ganglion (TG) neurons.ConclusionsThese data identify a key peripheral mechanism in cancer pain and highlight the clinical potential of specifically targeting nociceptors expressing both P2X2 and P2X3 subunits (e.g., P2X2/3 heterotrimers) to alleviate cancer pain.Electronic supplementary materialThe online version of this article (doi:10.1186/2051-5960-2-62) contains supplementary material, which is available to authorized users.

Animal Minds and Neuroimaging

As Colin Allen has argued, discussions between science and ethics about the mentality and moral status of nonhuman animals often stall on account of the fact that the properties that ethics presents as evidence of animal mentality and moral status, namely consciousness and sentience, are not observable "scientifically respectable" properties. In order to further discussion between science and ethics, it seems, therefore, that we need to identify properties that would satisfy both domains. In this article I examine the mentality and moral status of nonhuman animals from the perspective of neuroethics. By adopting this perspective, we can see how advances in neuroimaging regarding (1) research into the neurobiology of pain, (2) "brain reading," and (3) the minimally conscious state may enable us to identify properties that help bridge the gap between science and ethics, and hence help further the debate about the mentality and moral status of nonhuman animals.

Neural mechanisms underlying the pain of juvenile idiopathic arthritis

Pain is the most common symptom of juvenile idiopathic arthritis (JIA) and is arguably a more important factor in disability than the progression of the disease itself. Studies have highlighted the extent of this pain and its persistence in some young patients despite effective disease control. Understanding and effective management of pain in JIA is limited, and improved diagnosis and treatment would benefit from increased knowledge of the mechanisms underlying pain in childhood. This Review focuses upon the developmental neurobiology of pain, reviewing studies in animal models that increase clinical understanding and inform treatment of the painful manifestations of JIA. Pain processing in the juvenile nervous system differs from that in adults: nociceptive thresholds are lower and endogenous pain control systems are slow to mature. Furthermore, increasing evidence points to tissue injury in childhood having prolonged effects upon the developing pain system. Injury, inflammation and stress in early life can 'prime' peripheral nociceptors and central pain circuits, such that the pain associated with tissue inflammation is exacerbated in later life. A developmental, mechanism-based approach towards developing novel targets for the treatment of pain in JIA might therefore benefit the patient both as a child and as an adult if the disease recurs or persists.

Neurotrophin and endocannabinoid interactions in the neurobiology of pain

Neurotrophin and endocannabinoid interactions in the neurobiology of pain

Neurobiology of pain, interoception and emotional response: lessons from nerve growth factor‐dependent neurons

Although nerve growth factor (NGF) is a well-known neurotrophic factor, it also acts as a mediator of pain, itch and inflammation. Congenital insensitivity to pain with anhidrosis (CIPA) is an autosomal recessive genetic disorder caused by loss-of-function mutations in NTRK1, the gene encoding a receptor tyrosine kinase for NGF, TrkA. Mutations in NTRK1 cause the selective loss of NGF-dependent neurons in otherwise intact systems. NGF-dependent primary afferents are thinly myelinated Aδ or unmyelinated C-fibers that are dependent on the NGF-TrkA system during development. In CIPA, the lack of pain and the presence of anhidrosis (inability to sweat) are due to the absence of both NGF-dependent primary afferents and sympathetic postganglionic neurons, respectively. These peripheral neurons form an interface between the nervous system and the 'body-proper' and play essential roles in the interoception and sympathetic regulation of various tissues or organs. Patients with CIPA also show mental retardation and characteristic behaviors and are probably neuron-deficient within the brain. However, the functions of NGF-dependent neurons in the brain are controversial, both in animal and in human studies. This review focuses on various brain regions that express TrkA mRNA, based on data from the Allen Human Brain Atlas, and discusses putative neuronal networks related to these brain regions in humans. A better understanding the distribution of NGF-dependent neurons in the brain will provide a framework for further studies to investigate pain, interoception and emotional responses. Furthermore, strategies targeting the molecular mechanisms through which the NGF-TrkA system functions may provide hope for the development of novel analgesics.

The neurobiology of skeletal pain.

Disorders of the skeleton are one of the most common causes of chronic pain and long-term physical disability in the world. Chronic skeletal pain is caused by a remarkably diverse group of conditions including trauma-induced fracture, osteoarthritis, osteoporosis, low back pain, orthopedic procedures, celiac disease, sickle cell disease and bone cancer. While these disorders are diverse, what they share in common is that when chronic skeletal pain occurs in these disorders, there are currently few therapies that can fully control the pain without significant unwanted side effects. In this review we focus on recent advances in our knowledge concerning the unique population of primary afferent sensory nerve fibers that innervate the skeleton, the nociceptive and neuropathic mechanisms that are involved in driving skeletal pain, and the neurochemical and structural changes that can occur in sensory and sympathetic nerve fibers and the CNS in chronic skeletal pain. We also discuss therapies targeting nerve growth factor or sclerostin for treating skeletal pain. These therapies have provided unique insight into the factors that drive skeletal pain and the structural decline that occurs in the aging skeleton. We conclude by discussing how these advances have changed our understanding and potentially the therapeutic options for treating and/or preventing chronic pain in the injured, diseased and aged skeleton.

Beyond Rodent Models of Pain: Non-Human Primate Models for Evaluating Novel Analgesic Therapeutics and Elaborating Pain Mechanisms

Evaluation of potential analgesic therapeutics and the elaboration of the neurobiology of pain have heavily relied on pain models developed in rodents. However, a limitation of rodents is their phylogenetic distance from humans, which could in part account for the failure of some preclinical findings to translate to clinical utility. By contrast, given their genetic closeness and phenotypic similarities to humans, it is suggested that there be greater utilization of non-human primates (NHP) in preclinical pain studies. Methods to induce chronic pain-like states and quantify changes in nociception that have been developed in rodents could be adapted to the NHP. Similarly, human experimental injury-induced sensitization, which attempts to temporarily mimic the neuropathology and symptoms observed in the chronic pain state, could be adapted to the NHP. The NHP could then serve as a platform to validate human experimental models as well as proof-of-concept studies. Beyond experimentally modeled pain states, a number of naturally occurring disease states, such as osteoarthritis, are expressed by NHP, which could be utilized for both hypothesis testing and proof-of-concept studies. While NHP studies are logistically cumbersome, it is envisioned that NHP pain models will add value to current preclinical data and greatly facilitate the discovery of novel analgesic treatments.

Chronic multisite pain in major depression and bipolar disorder: cross-sectional study of 149,611 participants in UK Biobank

BackgroundChronic pain has a strong association with major depressive disorder (MDD), but there is a relative paucity of studies on the association between chronic multisite pain and bipolar disorder (BD). Such studies are required to help elucidate the complex biological and psychological overlap between pain and mood disorders. The aim of this study is to investigate the relationship between chronic multisite pain and mood disorder across the unipolar-bipolar spectrum.MethodsWe conducted a cross-sectional study of 149,611 UK Biobank participants. Self-reported depressive and bipolar features were used to categorise participants into MDD and BD groups and a non-mood disordered comparison group. Multinomial logistic regression was used to establish whether there was an association between extent of chronic pain (independent variable) and mood disorder category (dependent variable), using no pain as the referent category, and adjusting for a wide range of potential sociodemographic, lifestyle and comorbidity confounders.ResultsMultisite pain was significantly more prevalent in participants with BD and MDD, for example, 4–7 pain sites: BD 5.8%, MDD 4.5%, and comparison group 1.8% (p < 0.001). A relationship was observed between extent of chronic pain and risk of BD and persisted after adjusting for confounders (relative to individuals with no chronic pain): 2–3 sites RRR of BD 1.84 (95% CI 1.61, 2.11); 4–7 sites RRR of BD 2.39 (95% CI 1.88, 3.03) and widespread pain RRR of BD 2.37 (95% CI 1.73, 3.23). A similar relationship was observed between chronic pain and MDD: 2–3 sites RRR of MDD 1.59 (95% CI 1.54, 1.65); 4–7 sites RRR of MDD 2.13 (95% CI 1.98, 2.30); widespread pain RRR of MDD 1.86 (95% CI 1.66, 2.08).ConclusionsIndividuals who report chronic pain and multiple sites of pain are more likely to have MDD and are at higher risk of BD. These findings highlight an important aspect of comorbidity in MDD and BD and may have implications for understanding the shared neurobiology of chronic pain and mood disorders.

Sustained pain-related depression of behavior: effects of intraplantar formalin and complete freund's adjuvant on intracranial self-stimulation (ICSS) and endogenous kappa opioid biomarkers in rats.

BackgroundIntraplantar administration of complete Freund's adjuvant (CFA) and formalin are two noxious stimuli commonly used to produce sustained pain-related behaviors in rodents for research on neurobiology and treatment of pain. One clinically relevant manifestation of pain is depression of behavior and mood. This study compared effects of intraplantar CFA and formalin on depression of positively reinforced operant behavior in an assay of intracranial self-stimulation (ICSS) in rats. Effects of CFA and formalin on other physiological and behavioral measures, and opioid effects on formalin-induced depression of ICSS, were also examined.ResultsThere were four main findings. First, consistent with previous studies, both CFA and formalin produced similar paw swelling and mechanical hypersensitivity. Second, CFA produced weak and transient depression of ICSS, whereas formalin produced a more robust and sustained depression of ICSS that lasted at least 14 days. Third, formalin-induced depression of ICSS was reversed by morphine doses that did not significantly alter ICSS in saline-treated rats, suggesting that formalin effects on ICSS can be interpreted as an example of pain-related and analgesic-reversible depression of behavior. Finally, formalin-induced depression of ICSS was not associated with changes in central biomarkers for activation of endogenous kappa opioid systems, which have been implicated in depressive-like states in rodents, nor was it blocked by the kappa antagonist norbinaltorphimine.ConclusionsThese results suggest differential efficacy of sustained pain stimuli to depress brain reward function in rats as assessed with ICSS. Formalin-induced depression of ICSS does not appear to engage brain kappa opioid systems.Electronic supplementary materialThe online version of this article (doi:10.1186/1744-8069-10-62) contains supplementary material, which is available to authorized users.

The Use Of Neuropathic Pain Drugs In Patients With Sickle Cell Disease Is Associated With Older Age and Female Gender

BackgroundAlthough neuropathic pain is becoming an increasingly recognized component of sickle cell disease (SCD) pain, national data regarding the use of neuropathic pain drugs in SCD patients do not exist. Furthermore, factors associated with the development of neuropathic pain in SCD are not well characterized. In non-SCD pain populations, neuropathic pain is associated with older age and female gender. Older age is also associated with increased thermal pain sensitivity, a marker of neuropathic pain, in both SCD patients and pain populations without SCD. Thus, the objectives of our study were to describe the use of neuropathic pain drugs in children with SCD and determine factors associated with the use of these drugs. We hypothesized older age and female gender would be associated with increased use of neuropathic pain drugs. MethodsWe used the Pediatric Health Information System (PHIS) Database (2004-09) to investigate the use of neuropathic pain drugs in SCD patients during hospital admission. The PHIS provides comprehensive inpatient data, including detailed drug information, from 43 children's hospitals in the United States. All visits with a SCD-related (any genotype) ICD-9 discharge diagnosis (i.e., primary, secondary, tertiary) were included. To limit confounding, visits that included any psychiatric, seizure, or headache diagnosis in addition to a SCD diagnosis were excluded since neuropathic pain drugs also treat these disorders. The drugs of interest were based on published neuropathic pain treatment guidelines originally created for patients without SCD and included antiepileptics, tricyclic antidepressants, and selective serotonin reuptake inhibitors. Multivariate logistic regression analysis was used to determine the impact of age and gender on the use of neuropathic pain drugs with the outcome being whether a neuropathic pain drug was or was not prescribed during that admission. Age was classified into 4 groups (0-4, 5-10, 11-14, and 15-18 years) for clinical interpretation. ResultsA total of 61,325 visits met inclusion criteria. Mean age was 9.8 (±5.7) years. The proportions of visits in each age group were: 0-4 (24%), 5-10 (26%), 11-14 (22%), 15-18 (28%) and 49% were female. The majority had HbSS disease (73.7%). We found 3.6% were prescribed one or more neuropathic pain drugs with the majority (3.3%) receiving one drug. There was no difference in the use of neuropathic pain drugs over time (2004-09). The most commonly used drugs were: amitriptyline (47.4%), gabapentin (27.7%), phenytoin (12.3%), and fluoxetine (11.2%) with pregabalin, venlafaxine, paroxetine, and nortriptyline used infrequently. In multivariate analysis, compared to the reference group of 0-4 years, the odds of receiving a neuropathic pain drug increased significantly and sequentially for each older age group (Table 1). Female patients were more likely to be taking a neuropathic pain drug [OR 1.8 (CI 1.6-1.9; p<0.0001)]. There was no significant interaction between age and gender. ConclusionsNeuropathic pain drugs were infrequently prescribed (<5% of visits) which could reflect the lack of awareness of neuropathic pain in SCD during the time frame of the study. As hypothesized, older age and female gender were both significant independent predictors of neuropathic pain drug use with adolescents being almost 22 times more likely to be prescribed one of these drugs. The association between older age and neuropathic pain is supported by data in both SCD patients and non-SCD pain populations that reveal older age is associated with increased thermal pain sensitivity, a marker of neuropathic pain. This relationship suggests that SCD may have an effect on pain processing that worsens with age and also suggests that older patients have refractory pain requiring alternative drugs to opioids. Increased use of neuropathic pain drugs in females is also consistent with data in non-SCD pain populations and in SCD mice. The underlying reason for the relationship between age, gender and neuropathic pain in SCD warrants further investigation and may provide clues to the underlying neurobiology of SCD pain and help target treatment to the most at risk patients. Disclosures:No relevant conflicts of interest to declare.

Multiple sclerosis-induced neuropathic pain: pharmacological management and pathophysiological insights from rodent EAE models.

In patients with multiple sclerosis (MS), pain is a frequent and disabling symptom. The prevalence is in the range 29–86 % depending upon the assessment protocols utilised and the definition of pain applied. Neuropathic pain that develops secondary to demyelination, neuroinflammation and axonal damage in the central nervous system is the most distressing and difficult type of pain to treat. Although dysaesthetic extremity pain, L’hermitte’s sign and trigeminal neuralgia are the most common neuropathic pain conditions reported by patients with MS, research directed at gaining insight into the complex mechanisms underpinning the pathobiology of MS-associated neuropathic pain is in its relative infancy. By contrast, there is a wealth of knowledge on the neurobiology of neuropathic pain induced by peripheral nerve injury. To date, the majority of research in the MS field has used rodent models of experimental autoimmune encephalomyelitis (EAE) as these models have many clinical and neuropathological features in common with those observed in patients with MS. However, it is only relatively recently that EAE-rodents have been utilised to investigate the mechanisms contributing to the development and maintenance of MS-associated central neuropathic pain. Importantly, EAE-rodent models exhibit pro-nociceptive behaviours predominantly in the lower extremities (tail and hindlimbs) as seen clinically in patients with MS-neuropathic pain. Herein, we review research to date on the pathophysiological mechanisms underpinning MS-associated neuropathic pain as well as the pharmacological management of this condition. We also identify knowledge gaps to guide future research in this important field.

Editorial (Thematic Issue: Advances in Research on Pharmacological Targets for Pain Relief)

Several years ago, a former hot topic volume of Current Neuropharmacology assembled elegant reviews and perspectives that summarized and discussed state-of-the-art advances in research on the neurobiology of pain [1]. The current topography of the field is highlighting the need for new updates of scientific achievements and their pharmacological prospects. Viewpoints and technologies evaluating pain states have gradually evolved and novel pain target molecules are emerging. Newly discovered molecules shed light on future developments of promising pharmacological approaches. Accordingly, this issue collected highly insightful and informative reviews reflecting the many aspects of progress in the pain research. In the first review, Dr. Enrique J. Cobos and Dr. Enrique Portillo-Salido asked essential questions regarding the translational processes in the assessment of pharmacological potencies and efficacies. They sought to revise both our focus and view on the examination of therapeutic prospects during the preclinical period by intensively discussing the validity of pain assessment systems. Dr. Fumimasa Amaya, Dr. Yuta Izumi, Dr. Mika Sasaki, and Dr. Megumi Matsuda introduced a variety of pro-nociceptive mediators generated under injury conditions and discussed the associated mechanisms that drive pain hypersensitivity at the peripheral level and the validity of the molecular components as pharmacological targets. In the following review, Dr. Nicolas Cenac emphasized the crucial roles of protease-activated receptors and their signal transductions in visceral pain from the gut, pancreas and bladder as well as in functional bowel disorders. Dr. Seungkyu Lee described pain transmission and plasticity via the action of various neuronal voltage-gated calcium channels. Furthermore, for their inhibitors ranging from traditional to atypical ones, detailed molecular mechanisms and beneficial outcomes for chronic pain were summarized. The role of potassium channels is as important as that of excitatory ion channels in nociceptive firing. Dr. Nikita Gamper and Dr. Xiaona Du highlighted potassium channels as validated pain targets by extensive examination of evidence from molecular biology, physiology, and pharmacology. Very recently, the calcium-activated anion channel Anoctamin 1 made its debut as an important transducer for thermal pain and inflammatory mediator-induced pain. Dr. Hawon Cho and Dr. Uhtaek Oh, the researchers who first discovered this ion channel molecule, offered an in-depth analysis of its role in peripheral pain sensation. The importance of sensory TRP channels in the pain killing strategies has been established over the course of a decade. Dr. Hongzhen Hu, Dr. Jialie Luo, Dr. Edgar T. Walters, and Dr. Susan M. Carlton provided a review concerned with major issues regarding the TRP-mediated pain and their synthetic ligands. Resolvins and related omega-3-derived lipid substances are emerging as pro-resolving and anti-inflammatory mediators. Lastly, Dr. Sun Wook Hwang, Dr. Sungjae Yoo, and Dr. Ji Yeon Lim discussed their pain-killing aspects and druggability by reviewing recent results from analgesic assessments. The series of excellent reviews presented in this special issue will lead to a comprehensive understanding of the current trends in pain physiology and pharmacology research. Furthermore, hopefully this volume will help readers to generate future creative pain hypotheses, and to propose practical insights aimed at developing novel painkilling strategies.

Spirituality and Religion in Pain and Pain Management.

Pain relief is a management problem for many patients, their families, and the medical professionals caring for them. Although everyone experiences pain to some degree, responses to it vary from one person to another. Recognizing and specifying someone else’s pain is clinically a well know challenge. Research on the biology and neurobiology of pain has given us a relationship between spirituality and pain. There is growing recognition that persistent pain is a complex and multidimensional experience stemming from the interrelations among biological, psychological, social, and spiritual factors. Patients with pain use a number of cognitive and behavioral strategies to cope with their pain, including religious/spiritual factors, such as prayers, and seeking spiritual support to manage their pain. This article provides an overview of the complex phenomenon of pain, with a focus on spiritual and religious issues in pain management.

Spirituality and religion in pain and pain management

Pain relief is a management problem for many patients, their families, and the medical professionals caring for them. Although everyone experiences pain to some degree, responses to it vary from one person to another. Recognizing and specifying someone else’s pain is clinically a well know challenge. Research on the biology and neurobiology of pain has given us a relationship between spirituality and pain. There is growing recognition that persistent pain is a complex and multidimensional experience stemming from the interrelations among biological, psychological, social, and spiritual factors. Patients with pain use a number of cognitive and behavioral strategies to cope with their pain, including religious/spiritual factors, such as prayers, and seeking spiritual support to manage their pain. This article provides an overview of the complex phenomenon of pain, with a focus on spiritual and religious issues in pain management.

Juvenile Idiopathic Arthritis and Pain — More Than Simple Nociception

Pain is a very common and sometimes limiting symptom in patients with juvenile idiopathic arthritis (JIA). Nonetheless, there remain many unanswered questions regarding pain perception in JIA and the neurobiology of pain in this disease. In this edition of The Journal , Leegaard, et al 1 report their findings of lowered pain threshold in patients with JIA that add to our understanding of a fundamental aspect of this disease manifestation in JIA. The disease pattern for JIA tends to follow a course of quiescent periods with disease activity flares superimposed. Some children have unrelenting disease activity that may be resistant to therapeutic interventions. Treatment of JIA is often complex and relies on medications, allied health interventions, and multidisciplinary expertise, ideally delivered in a coordinated manner in a predominantly ambulatory setting. JIA may have a profound influence on children’s lives and their experience of pain may be central to this2,3. Studies have found that reduced quality of life and functional outcome (social, emotional, and physical), lowered mood, and poor sleep are all associated with higher levels of pain perception in JIA4,5,6. Pain in JIA has historically been underreported, under-recognized, and underresearched, with clinical and research focus on inflammation, damage, and function. There are few specific or multidimensional and reliable pain assessment tools7, which has limited clinical research. Thus, the evidence base for pain management has traditionally relied upon extrapolation from adult medicine8. By enriching our understanding of the neurobiology of pain pathways in JIA, the predictive factors for those young people most vulnerable to pain, in conjunction with a focus on developing effective treatments, we will make inroads into one of the most significant symptoms for our patients with JIA. While there are many studies … Address correspondence to Dr. Singh-Grewal; E-mail: davinder.singhgrewal{at}health.nsw.gov.au

Ask the Experts: Peripheral and Central Mechanisms of Chronic Musculoskeletal Pain

Dr Sluka is a professor in the Department of Physical Therapy and Rehabilitation Science at the University of Iowa (IA, USA). She is also a member of the Pain Research Program and the Neuroscience Graduate Program. She received a physical therapy degree from Georgia State University (GA, USA) and practiced physical therapy pain management in Houston (TX, USA) before obtaining a PhD in Anatomy from the University of Texas Medical Branch in Galveston (TX, USA). After a postdoctoral fellowship with Dr William D Willis, she joined the faculty at the University of Iowa. Dr Sluka’s research focuses on the neurobiology of musculoskeletal pain, as well as the mechanisms and effectiveness of nonpharmacological pain treatments commonly used by physical therapists. She has published over 140 peer-reviewed manuscripts, numerous book chapters and a textbook on Pain Mechanisms and Management for the Physical Therapist. She has received numerous awards including the Marian Williams Award for Research in Physical Therapy and is a Catherine Worthingham Fellow from the American Physical Therapy Association and the Frederick WL Kerr Basic Science Research Award from the American Pain Society. She is actively involved in the International Association for the Study of Pain, the American Pain Society and the American Physical Therapy Association, serving on committees, task forces and society boards.