Persistent Pain Conditions Research Articles

Bedside Neuromodulation of Persistent Pain and Allodynia with Caloric Vestibular Stimulation.

Caloric vestibular stimulation (CVS) is a well-established neurological diagnostic technique that also induces many phenomenological modulations, including reductions in phantom limb pain (PLP), spinal cord injury pain (SCIP), and central post-stroke pain. We aimed to assess in a variety of persistent pain (PP) conditions (i) short-term pain modulation by CVS relative to a forehead ice pack cold-arousal control procedure and (ii) the duration and repeatability of CVS modulations. The tolerability of CVS was also assessed and has been reported separately. We conducted a convenience-based non-randomised single-blinded placebo-controlled study. Thirty-eight PP patients were assessed (PLP, n = 8; SCIP, n = 12; complex regional pain syndrome, CRPS, n = 14; non-specific PP, n = 4). Patients underwent 1-3 separate-day sessions of iced-water right-ear CVS. All but four also underwent the ice pack procedure. Analyses used patient-reported numerical rating scale pain intensity (NRS-PI) scores for pain and allodynia. Across all groups, NRS-PI for pain was significantly lower within 30 min post-CVS than post-ice pack (p < 0.01). Average reductions were 24.8% (CVS) and 6.4% (ice pack). CRPS appeared most responsive to CVS, while PLP and SCIP responses were less than expected from previous reports. The strongest CVS pain reductions lasted hours to over three weeks. CVS also induced substantial reductions in allodynia in three of nine allodynic CRPS patients, lasting 24 h to 1 month. As reported elsewhere, only one patient experienced emesis and CVS was widely rated by patients as a tolerable PP management intervention. Although these results require interpretative caution, CVS was found to modulate pain relative to an ice pack control. CVS also modulated allodynia in some cases. CVS should be examined for pain management efficacy using randomised controlled trials.

Investigation of the effect of catechol-o-methyltransferase gene rs4680 polymorphism on trigeminal neuralgia susceptibility

Research has been conducted to explore the genetic basis of trigeminal neuralgia, a persistent pain condition that impacts the trigeminal nerve. COMT is an enzyme responsible for inactivating substances and hormones containing catechol and catecholamines. Previous research has linked COMT gene polymorphism with various pain conditions, including migraine. Our research aimed to investigate the correlation between trigeminal neuralgia and the rs4680 polymorphism of the COMT gene. We conducted a research project which included 10 individuals diagnosed with trigeminal neuralgia and 30 healthy individuals as controls. Following collection of blood samples, we isolated DNA from the samples and then genotyping of COMT rs4680 polymorphism was performed with Real-Time PCR, using TaqMan SNP Genotyping Assay. Among the trigeminal neuralgia patients, 2 of them exhibited the AA genotype, 6 had the AG genotype, and 2 had the GG genotype for COMT rs4680. The AG genotype was notably prevalent. No statistically significant differences in the distributions of COMT genotypes and allele frequencies were found between the experimental (patients) and the control group. However, the AG genotype appeared to be more frequent in the patient group. Moving forward, we plan to expand our study by increasing the number of patients and control subjects. This will enable us to further elucidate the potential relationship between COMT gene polymorphism and trigeminal neuralgia.

Evolving Concepts of Pain Management in Elderly Patients.

The elderly population typically suffer from a variety of diseases that mostly reflect the degenerative changes linked with the aging process. These diseases may be exacerbated by acute pain or by an abrupt aggravation of previously stable chronic pain. Physical and psychological changes associated with aging may influence one's experience of pain and, as a result, the severity of pain. Pain treatment in the elderly can be complex and is often a budgetary burden on the nation's health care system. These difficulties arise, in part, because of unanticipated pharmacodynamics, changed pharmacokinetics, and polypharmacy interactions. Therefore, it is critical to integrate a multidisciplinary team to develop a management strategy that incorporates medical, psychological, and surgical methods to control persistent pain conditions. It is in this critical process that pain prediction models can be of great use. The purpose of pain prediction models for the elderly is the use of mathematical models to predict the occurrence and intensity of pain and pain-related conditions. These mathematical models employ a vast quantity of data to ascertain the many risk factors for the development of pain problems in the elderly, whether said risks are adjustable or not. These models will pave the way for more informed medical decision making that are based on the findings of thousands of patients who have previously experienced the same illness and related pain conditions. However, future additional research needs to be undertaken to build prediction models that are not constrained by substantial legal or methodological limitations.

Unravelling interacting barriers and facilitators to adherence and delivery of exercise-based care in the treatment of Subacromial Pain Syndrome – an exploratory qualitative study

Purpose Subacromial Pain Syndrome (SAPS) is a common persistent pain condition. Exercise-based care is first-line recommendation, but an insufficient exercise dose hampers effectiveness. This study explores individual and contextual barriers and facilitators for delivery of and adherence to exercise-based care in people with SAPS. Materials and Methods Participants in this exploratory qualitative study were involved in the management of SAPS in Denmark. Triangular interviews and analyses were conducted within 3 themes (delivery of recommended services, adherence to recommendations, and frames of the clinical pathways) using the Theoretical Domains Framework (TDF) and the Behavioural Change Wheel model (BCW) to map barriers and facilitators into the Capability, Opportunity, Motivation and Behaviour (COM-B) model. Results From interviews with 10 persons with SAPS and 37 healthcare practitioners and double-deductive analyses, 30 subjects of target behaviour within 13 TDF domains emerged across perspectives and COM-B components. Central barriers to delivery and adherence were inconsistencies in diagnostic terminology, cross-professional disagreements, beliefs, and expectations towards pathway services. Conclusion We identified interrelated individual and contextual barriers to delivery and adherence across all aspects of the BCW, underpinning the complexity of the subject. Findings support that effectiveness of exercise-based care is linked to contextual barriers to delivery and adherence.

Revealing a role of brainstem monoaminergic nuclei on the pronociceptive effect of sleep restriction

Sleep disturbances and persistent pain conditions are public health challenges worldwide. Although it is well-known that sleep deficit increases pain sensitivity, the underlying mechanisms remain elusive. We have recently demonstrated the involvement of nucleus accumbens (NAc) and anterior cingulate cortex (ACC) in the pronociceptive effect of sleep restriction. In this study, we found that sleep restriction increases c-Fos expression in NAc and ACC, suggesting hyperactivation of these regions during prolonged wakefulness in male Wistar rats. Blocking adenosine A2A receptors in the NAc or GABAA receptors in the ventral tegmental area (VTA), dorsal raphe nucleus (DRN), or locus coeruleus (LC) effectively mitigated the pronociceptive effect of sleep restriction. In contrast, the blockade of GABAA receptors in each of these nuclei only transiently reduced carrageenan-induced hyperalgesia. Pharmacological activation of dopamine D2, serotonin 5-HT1A and noradrenaline alpha-2 receptors within the ACC also prevented the pronociceptive effect of sleep restriction. While pharmacological inhibition of these same monoaminergic receptors in the ACC restored the pronociceptive effect which had been prevented by the GABAergic disinhibition of the of the VTA, DRN or LC. Overall, these findings suggest that the pronociceptive effect of sleep restriction relies on increased adenosinergic activity on NAc, heightened GABAergic activity in VTA, DRN, and LC, and reduced inhibitory monoaminergic activity on ACC. These findings advance our understanding of the interplay between sleep and pain, shedding light on potential NAc-brainstem-ACC mechanisms that could mediate increased pain sensitivity under conditions of sleep impairment.

Experience of compassion-based practice in mindfulness for health for individuals with persistent pain.

Research indicates that acquiring compassion is an integral part to positive outcomes to Mindfulness-based interventions (MBI), yet there is both theoretic and empirical literature suggesting that people with persistent pain are more likely to experience challenges and distress when engaging compassion-based practices. Mindfulness for Health is a standardised MBI for people with persistent pain and health conditions. This study sought to explore the positive, neutral and difficult experiences of compassion-based practice and meditation for participants in Mindfulness for Health to further understand implications and risks for participants of MBI's. A qualitative design using Interpretative Phenomenological Analysis was applied to explore how participants understood of the experience of compassion-based practice and the meaning they gave to it. Eight participants who had completed the Mindfulness for Health from four separate groups were interviewed about their experience. Five master themes were identified 'turning away from self-with-pain', 'self-with-pain experienced as shameful', 'facilitating change', 'turning towards self-with-pain', and 'accepting self'. Participants identified both perceived positive changes and difficult emotional experiences during the meditation practice, which they related to the context of compassion in their past and present life. Developing compassion is an important part of Mindfulness for Health, which is salient for participants as both a challenging and potentially valuable experience. Acquisition of mindfulness skills, supporting group dynamics and modelling compassion are understood as helpful in overcoming personal barriers and challenging experiences. Further research is needed to understand processes involved and explore the experience of non-completers.

A199 ALKAL2/ALK AXIS PROMOTE PERSISTENT VISCERAL PAIN

Abstract Background Long-lasting changes in neural pain circuits precipitate the transition from acute to chronic pain in patients living with inflammatory bowel diseases (IBDs). While significant improvement in IBD therapy has been made to reduce inflammation, a large subset of patients continues to suffer throughout quiescent phases of the disease. Peripheral and central mechanisms contribute to the transition from acute to chronic pain during clinical remission. In the search of new treatments, we previously found that targeting the anaplastic lymphoma kinase (ALK) receptor could have therapeutic value for persistent pain conditions. Aims Here we investigated whether ALKAL2 (ALK ligand) /ALK signaling axis regulates chronic visceral pain. Methods We used the post-inflammatory dextran sodium sulfate (DSS) mouse model of colitis as a well-established rodent model of chronic visceral pain, in which animals display increased VHS 5 weeks after DSS administration in the absence of inflammation as described in IBD patients. To assess the role of ALKAL2/ALK signalling in chronic visceral pain, we pharmacologically blocked ALK receptor using clinically available compound Lorlatinib in the postcolitis model. Moreover we genetically depleted ALKAL2 in gut-innervating nociceptors that express the heat sensitive transient receptor potential vanilloid type 1 (TRPV1) channel, using shRNA vectorized in cell type specific Adeno-associated Viruses. Results We showed that ALKAL2 expression was significatively enhanced in lumbosacral (LS) dorsal root ganglia (DRG) sensory neurons in the post-colitis model. In naïve mice, ALKAL2 administration induced visceral hypersensitivity in an ALK dependant manner. In addition, depletion of ALKAL2 in TRPV1 nociceptors or blocking ALK with the clinically available compound Lorlatinib, reversed visceral hypersensitivity in the post-colitis model. Accordingly, phosphorylation of ALK receptor occurring at the LS of the spinal dorsal horn was reduced. Conclusions Overall, these findings provide novel insights into the mechanisms underlying the transition from acute to chronic visceral pain in IBD. Our work could generate a portfolio of clinically available anti-cancer drugs, including Lorlatinib, as novel pain therapeutics. Repurposed ALK inhibitor could facilitate pain management in in individuals with IBD. Funding Agencies CIHR

Readiness of nociceptor cell bodies to generate spontaneous activity results from background activity of diverse ion channels and high input resistance.

Nociceptor cell bodies generate "spontaneous" discharge that can promote ongoing pain in persistent pain conditions. Little is known about the underlying mechanisms. Recordings from nociceptor cell bodies (somata) dissociated from rodent and human dorsal root ganglia have shown that previous pain in vivo is associated with low-frequency discharge controlled by irregular depolarizing spontaneous fluctuations of membrane potential (DSFs), likely produced by transient inward currents across the somal input resistance. Using mouse nociceptors, we show that DSFs are associated with high somal input resistance over a wide range of membrane potentials, including depolarized levels where DSFs approach action potential (AP) threshold. Input resistance and both the amplitude and frequency of DSFs were increased in neurons exhibiting spontaneous activity. Ion substitution experiments indicated that the depolarizing phase of DSFs is generated by spontaneous opening of channels permeable to Na + or Ca 2+ and that Ca 2+ -permeable channels are especially important for larger DSFs. Partial reduction of the amplitude or frequency of DSFs by perfusion of pharmacological inhibitors indicated small but significant contributions from Nav1.7, Nav1.8, TRPV1, TRPA1, TRPM4, and N-type Ca 2+ channels. Less specific blockers suggested a contribution from NALCN channels, and global knockout suggested a role for Nav1.9. The combination of high somal input resistance plus background activity of diverse ion channels permeable to Na + or Ca 2+ produces DSFs that are poised to reach AP threshold if resting membrane potential depolarizes, AP threshold decreases, or DSFs become enhanced-all of which can occur under painful neuropathic and inflammatory conditions.

Characterization of Common Genetic Variants in P2RX7 and Their Contribution to Chronic Pain Conditions

The adenosine triphosphate (ATP)-gated channel P2X7 is encoded by a gene enriched for common nonsynonymous variants. Many of these variants have functional cellular effects, and some have been implicated in chronic pain. In this study, we first systematically characterized all 17 common nonsynonymous variants using whole-cell patch clamp electrophysiology. Then, we analyzed these variants for statistical association with chronic pain phenotypes using both individual P2RX7 variants as predictors and cumulative allele counts of same-direction cellular effect in univariate models. Association and validation analyses were conducted in the Orofacial Pain: Prospective Evaluation and Risk Assessment (OPPERA) cohort (N = 3260) and in the Complex Persistent Pain Conditions (CPPC) cohort (N = 900), respectively. Our results showed an association between allele A of rs7958311 and an increased risk of chronic pelvic pain, with convergent evidence for contribution to fibromyalgia and irritable bowel syndrome, confirmed in a meta-analysis. This allelic variant produced a unique cellular phenotype: a gain-of-function in channel opening, and a loss-of-function in pore opening. A computational study using a 12-state Markov model of ATP binding to the P2X7 receptor suggested that this cellular phenotype arises from an increased ATP binding affinity and an increased open channel conductance combined with a loss of sensitization. Cumulative allele count analysis did not provide additional insights. In conclusion, our results go beyond reproducing association for rs7958311 with chronic pain and suggest that its unique combination of gain-of-function in channel and loss-of-function in pore activity may explain why it is likely the only common P2RX7 variant with contribution to chronic pain. PerspectiveThis study characterizes all common P2RX7 variants using cellular assays and statistical association analyses with chronic pain, with Markov state modeling of the most robustly associated variant.

Sleep and Pain: A Role for the Anterior Cingulate Cortex, Nucleus Accumbens, and Dopamine in the Increased Pain Sensitivity Following Sleep Restriction

Persistent pain conditions and sleep disorders are public health problems worldwide. It is widely accepted that sleep disruption increases pain sensitivity; however, the underlying mechanisms are poorly understood. In this study, we used a protocol of 6 hours a day of total sleep deprivation for 3 days in rats to advance the understanding of these mechanisms. We focused on gender differences and the dopaminergic mesocorticolimbic system. The findings demonstrated that sleep restriction (SR) increased pain sensitivity in a similar way in males and females, without inducing a significant stress response. This pronociceptive effect depends on a nucleus accumbens (NAc) neuronal ensemble recruited during SR and on the integrity of the anterior cingulate cortex (ACC). Data on indirect dopaminergic parameters, dopamine transporter glycosylation, and dopamine and cyclic adenosine monophosphate (AMP)-regulated phosphoprotein-32 phosphorylation, as well as dopamine, serotonin, and norepinephrine levels, suggest that dopaminergic function decreases in the NAc and ACC after SR. Complementarily, pharmacological activation of dopamine D2, but not D1 receptors either in the ACC or in the NAc prevents SR from increasing pain sensitivity. The ACC and NAc are the main targets of dopaminergic mesocorticolimbic projections with a key role in pain modulation. This study showed their integrative role in the pronociceptive effect of SR, pointing to dopamine D2 receptors as a potential target for pain management in patients with sleep disorders. These findings narrow the focus of future studies on the mechanisms by which sleep impairment increases pain sensitivity. PerspectiveThis study demonstrates that the pronociceptive effect of SR affects similarly males and females and depends on a NAc neuronal ensemble recruited during SR and on the integrity of the ACC. Findings on dopaminergic function support dopamine D2 receptors as targets for pain management in sleep disorders patients.

An international study to explore the feasibility of collecting standardised outcome data for Complex Regional Pain Syndrome: recommendations for an international clinical research registry.

Complex Regional Pain Syndrome (CRPS) is a persistent pain condition with low prevalence. Multi-centre collaborative research is needed to attain sufficient sample sizes for meaningful studies. This international observational study: (1) tested the feasibility and acceptability of collecting outcome data using an agreed core measurement set (2) tested and refined an electronic data management system to collect and manage the data. Adults with CRPS, meeting the Budapest diagnostic clinical criteria, were recruited to the study from 7 international research centres. After informed consent, a questionnaire comprising the core set outcome measures was completed: on paper at baseline (T1), and at 3 or 6 months (T2) using a paper or e-version. Participants and clinicians provided feedback on the data collection process. Clinicians completed the CRPS severity score at T1 and optionally, at T2. Ethical approval was obtained at each international centre. Ninety-eight adults were recruited (female n=66; mean age 46.6 years, range 19-89), of whom 32% chose to receive the T2 questionnaire in an electronic format. Fifty-five participants completed both T1 and T2. Eighteen participants and nine clinicians provided feedback on their data collection experience. This study confirmed the questionnaire core outcome data are feasible and practicable to collect in clinical practice. The electronic data management system provided a robust means of collecting and managing the data across an international population. The findings have informed the final data collection tools and processes which will comprise the first international, clinical research registry and data bank for CRPS.

Acute Transcriptomic and Epigenetic Alterations at T12 After Rat T10 Spinal Cord Contusive Injury.

Spinal cord injury is a severely debilitating condition affecting a significant population in the USA. Spinal cord injury patients often have increased risk of developing persistent neuropathic pain and other neurodegenerative conditions beyond the primary lesion center later in their life. The molecular mechanism conferring to the "latent" damages at distal tissues, however, remains elusive. Here, we studied molecular changes conferring abnormal functionality at distal spinal cord (T12) beyond the lesion center (T10) by combining next-generation sequencing (RNA- and bisulfite sequencing), super-resolution microscopy, and immunofluorescence staining at 7days post injury. We observed significant transcriptomic changes primarily enriched in neuroinflammation and synaptogenesis associated pathways. Transcription factors (TFs) that regulate neurogenesis and neuron plasticity, including Egr1, Klf4, and Myc, are significantly upregulated. Along with global changes in chromatin arrangements and DNA methylation, including 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC), bisulfite sequencing further reveals the involvement of DNA methylation changes in regulating cytokine, growth factor, and ion channel expression. Collectively, our results pave the way towards understanding transcriptomic and epigenomic mechanism in conferring long-term disease risks at distal tissues away from the primary lesion center and shed light on potential molecular targets that govern the regulatory mechanism at distal spinal cord tissues.

Towards improved sexual health among women with provoked vestibulodynia: experiences from a somatocognitive therapy approach

Purpose Provoked vestibulodynia (PVD) is a common reason for sexual pain in young women. Furthermore, this persistent vulvar pain condition can have a significant negative impact on an individual’s sexual health and well-being. As knowledge about effective treatments is limited, the aim of this study was to gain insight into meaningful processes towards improved sexual health, supported by a multimodal physiotherapy intervention. Methods Through individual semi-structured interviews, this longitudinal, qualitative study explored the experiences of ten young women with PVD who took part in a somatocognitive therapy program. Participants were interviewed towards the end of their therapy period, and again one year later, to develop insight into therapeutic processes unfolding over time. Results Through analysis we identified the following themes: (1) Developing positive feelings of embodiment, (2) Developing a greater awareness of internal feelings and bodily states, and (3) Developing sex-positive beliefs and behaviours. Conclusion The findings show how individually tailored physiotherapy emphasising embodiment and sexual health can promote meaningful processes towards improved sexual health for women living with PVD.

Accumulation of health complaints is associated with persistent musculoskeletal pain two years later in adolescents: The Fit Futures study.

There is limited knowledge on the association between different health complaints and the development of persistent musculoskeletal pain in adolescents. The aims of this study were to assess whether specific health complaints, and an accumulation of health complaints, in the first year of upper-secondary school, were associated with persistent musculoskeletal pain 2 years later. We used data from a population-based cohort study (the Fit Futures Study in Norway), including 551 adolescents without persistent musculoskeletal pain at baseline. The outcome was persistent musculoskeletal pain (≥3 months) 2 years after inclusion. The following self-reported health complaints were investigated as individual exposures at baseline: asthma, allergic rhinitis, atopic eczema, headache, abdominal pain and psychological distress. We also investigated the association between the accumulated number of self-reported health complaints and persistent musculoskeletal pain 2 years later. Logistic regression analyses estimated adjusted odds ratios (ORs) with 95% confidence intervals (CIs). At the 2-year follow-up, 13.8% (95% CI [11.2-16.9]) reported persistent musculoskeletal pain. Baseline abdominal pain was associated with persistent musculoskeletal pain 2 years later (OR 2.33, 95% CI [1.29-4.19], p = 0.01). Our analyses showed no statistically significant associations between asthma, allergic rhinitis, atopic eczema, headache or psychological distress and persistent musculoskeletal pain at the 2-year follow-up. For the accumulated number of health complaints, a higher odds of persistent musculoskeletal pain at the 2-year follow-up was observed for each additional health complaint at baseline (OR 1.33, 95% CI [1.07-1.66], p = 0.01). Health care providers might need to take preventive actions in adolescents with abdominal pain and in adolescents with an accumulation of health complaints to prevent development of persistent musculoskeletal pain. The potential multimorbidity perspective of adolescent musculoskeletal pain is an important topic for future research to understand the underlying patterns of persistent pain conditions in adolescents.

Outcomes of Workers’ Compensation Patients Undergoing Neuromodulation for Persistent Neuropathic Pain Conditions

Workers’ compensation patients have long been identified as having worse outcomes with interventional and surgical therapies. Patients who develop persistent neuropathic pain conditions may benefit from spinal cord stimulation or dorsal root ganglion stimulation, which has shown to be more beneficial than conventional medical management. The efficacy of these modalities in workers’ compensation patients has been questioned, and it remains to be seen how this population responds to neuromodulation in various functional domains.

Persistent pain and long-term physical and mental conditions and their association with psychological well-being; data from 10,744 individuals from the Lolland-Falster health study.

Persistent pain (PP) and long-term conditions are all associated with psychological well-being. Less is known about their associations with reduced psychological well-being when co-occurring. We investigated how PP and long-term physical and mental conditions relate to psychological well-being when occurring together. Data collected in the Danish population-based Lolland-Falster Health study were used in this cross-sectional study. Participants aged ≥18years completing questions concerning PP, long-term conditions and psychological well-being were included. PP and long-term conditions were defined as conditions lasting 6months or longer. Psychological well-being was assessed by the World Health Organization Well-Being Index (WHO-5). Multiple linear regression investigated combinations of PP and physical and mental long-term conditions and their associations with WHO-5. Of 11,711 participants, 10,744 had available data. One third had PP (n = 3250), while 6144 (57%), 213 (2%) and 946 (9%) reported having only physical conditions, only mental conditions or both, respectively. All combinations of PP and long-term conditions were negatively associated with WHO-5. PP in combination with mental (-23.1 (95% CI -28.3 to -17.8)) or both physical and mental conditions (-25.1 (-26.7 to -23.52) yielded the strongest negative associations. Two or more pain sites together with long-term physical and mental conditions was associated with a lower WHO-5 score (-6.2 (-8.9 to -3.5) compared to none or one pain site. The presence of PP and long-term conditions, in particular mental conditions, were strongly associated with worse psychological well-being. This highlights the importance of assessing psychological well-being in individuals with PP and long-term conditions.

PO165 / #732 OUTCOMES OF WORKERS’ COMPENSATION PATIENTS UNDERGOING NEUROMODULATION FOR PERSISTENT NEUROPATHIC PAIN CONDITIONS: E-POSTER VIEWING

Workers’ compensation patients have long been identified as having worse outcomes with interventional and surgical therapies. Patients who develop persistent neuropathic pain conditions may benefit from spinal cord stimulation or dorsal root ganglion stimulation, which has shown to be more beneficial than conventional medical management. The efficacy of these modalities in workers’ compensation patients has been questioned, and it remains to be seen how this population responds to neuromodulation in various functional domains.

Perturbations in Neuroinflammatory Pathways Are Associated With a Worst Pain Profile in Oncology Patients Receiving Chemotherapy

Unrelieved pain occurs in 55% of cancer patients. Identification of molecular mechanisms for pain may provide insights into therapeutic targets. Purpose was to evaluate for perturbations in neuroinflammatory pathways between oncology patients with and without severe pain. Worst pain severity was rated using a 0 to 10 numeric rating scale six times over two cycles of chemotherapy. Latent profile analysis was used to identify subgroups of patients with distinct pain profiles. Pathway impact analyses were performed in two independent samples using gene expression data obtained from RNA sequencing (n = 192) and microarray (n = 197) technologies. Fisher's combined probability test was used to identify significantly perturbed pathways between None versus the Severe pain classes. In the RNA sequencing and microarray samples, 62.5% and 56.3% of patients were in the Severe pain class, respectively. Nine perturbed pathways were related to neuroinflammatory mechanisms (i.e., retrograde endocannabinoid signaling, gamma-aminobutyric acid synapse, glutamatergic synapse, Janus kinase-signal transducer and activator of transcription signaling, phagosome, complement and coagulation cascades, cytokine-cytokine receptor interaction, chemokine signaling, calcium signaling). First study to identify perturbations in neuroinflammatory pathways associated with severe pain in oncology outpatients. Findings suggest that complex neuroimmune interactions are involved in the maintenance of chronic pain conditions. PerspectiveIn this study that compared oncology patients with none versus severe pain, nine perturbed neuroinflammatory pathways were identified. Findings suggest that complex neuroimmune interactions are involved in the maintenance of persistent pain conditions.

Beyond pain in the brain: A clinician's guide to interpreting the spinal cord's role in the pain experience

IntroductionPhysical therapy practice has greatly improved in providing a biopsychosocial approach when considering persistent pain. However, the spinal cord is often overlooked as a structure with an important role in modulating nociceptive information. PurposeThis article highlights the role of the dorsal horn (DH) in nociceptive processing and its impact on persistent pain conditions as they appear clinically. Key processes occurring in the spinal cord are described, including cellular changes and local spinal network responses to nociceptive stimuli. Additionally, associated clinical symptoms are discussed and some aspects of physical therapy evaluation are challenged based on the mechanisms of nociceptive processing presented in this commentary. ImplicationsThe spinal cord is an active participant in nociceptive processing, directly impacting the intensity, spread, and recurrence of pain, including within the context of central sensitization. Changes in the behavior of DH neurons are possible with sufficient stimulation and may occur after injury. Additionally, spinal cord activation patterns may lead to bilateral symptoms given adequate strength and duration despite a single peripheral driver. Viewing the spinal cord as a dynamic structure capable of up or down regulating its response to stimuli gives the clinician a better understanding of the nervous system's complex response to prolonged nociceptive input.

Key Learning Statements for Persistent Pain Education: An Iterative Analysis of Consumer, Clinician and Researcher Perspectives and Development of Public Messaging

Over the last decade, the content, delivery and media of pain education have been adjusted in line with scientific discovery in pain and educational sciences, and in line with consumer perspectives. This paper describes a decade-long process of exploring consumer perspectives on pain science education concepts to inform clinician-derived educational updates (undertaken by the authors). Data were collected as part of a quality audit via a series of online surveys in which consent (non-specific) was obtained from consumers for their data to be used in published research. Consumers who presented for care for a persistent pain condition and were treated with a pain science education informed approach were invited to provide anonymous feedback about their current health status and pain journey experience 6, 12 or 18 months after initial assessment. Two-hundred eighteen consumers reported improvement in health status at follow-up. Results of the surveys from 3 cohorts of consumers that reported improvement were used to generate iterative versions of ‘Key Learning Statements’. Early iteration of these Key Learning Statements was used to inform the development of Target Concepts and associated community-targeted pain education resources for use in public health and health professional workforce capacity building initiatives. PerspectiveThis paper reflects an explicit interest in the insights of people who have been challenged by persistent pain and then recovered, to improve pain care. Identifying pain science concepts that consumers valued learning provided valuable information to inform resources for clinical interactions and community-targeted pain education campaigns.