Assessment and classification of peripheral pain in athletes: a scoping review protocol

Pain is often presumed to be part of the sport injury experience. The time-loss definition of injury leads to under-reported athletic pain impacting performance and quality of life. Whilst research regarding the assessment and classification of back pain in athletes is emerging, little has been reported regarding how peripheral pain is assessed and classified in research and practice. Six databases will be searched for relevant articles. Title and abstract screening followed by full-text screening will be completed by two independent reviewers. Data charting will be carried out using a modified standardised form. Descriptive results and frequencies will be reported. Pain measures identified in the studies will be mapped against the IOC Athlete Pain Framework alongside a narrative summary. Published peer-reviewed primary research studies alongside systematic reviews and clinical practice guidelines reporting the assessment or classification of pain in athletes of any age with chronic or acute peripheral pain across all study contexts in the English language on human participants from inception of the databases will be included. The results of this study are part of a body of research which will be used to inform the development of a pain assessment framework. The scoping review will be submitted for peer-reviewed journal publication and presented at sports medicine conferences. This review will inform researchers and clinicians working with athletes in pain how pain assessment and classification is currently conducted and positioned against the IOC Athlete Pain Framework.

Kappa Opioid Receptor Agonists: New Targets In The Treatment Of Pain

<p>Background and Purpose: Pain, although necessary for survival, can become pathological affecting an estimated 1 in 5 adults globally. It is also the most common reason people seek medical attention. Mu opioid receptor (MOPr) agonists, such as morphine, are the gold standard treatment for pain. Although these drugs have excellent analgesic properties, adverse effects such as addiction, tolerance and respiratory depression make their use problematic. An estimated 10,000 New Zealanders are addicted to prescription opiates, highlighting the need for better drugs to treat pain. Kappa opioid receptor (KOPr) agonists have analgesic properties and, unlike MOPr agonists, are also anti-addictive. Unfortunately, adverse effects such as sedation and dysphoria, have limited their therapeutic potential. The discovery of KOPr agonists that have analgesic properties without inducing adverse effects can allow for better, more efficient treatments of pain. We are the first to report the analgesic potential of novel Salvinorin A (Sal A) analogues: Tetrahydropyran Salvinorin A (THP Sal A) and Mesyl Salvinorin B (Mesyl Sal B). Experimental Approach and Compounds Tested: This study uses animal behavioural models to characterise the analgesic, anti-oedematous, sedative and hypothermic effects of a structurally new class of KOPr agonists including Sal A, THP Sal A and Mesyl Sal B. The known peripherally restricted KOPr agonist, ICI 204,448, was used to evaluate the peripherally mediated analgesic mechanisms of KOPr agonists. The tail-flick and intradermal formalin test were used to assess acute central and peripheral pain processes respectively. Sedative effects were monitored via rotarod performance test; thermoregulatory effects were also recorded. Key Results: ICI 204,448 attenuated inflammatory pain at a dose of 1 mg/kg (P<0.05, 30 min) and 2 mg/kg (P<0.001, 30-35 min). Although it showed no centrally mediated analgesic effects, it was found to be sedative at a dose of 2 mg/kg (P<0.01, 15-60 min). Sal A (2 mg/kg) attenuated inflammatory pain (P<0.01, 25-35 min) at the same dose it was sedative (P<0.01, 2-15 min). Although it treated acute thermal pain at a non-sedative dose (1 mg/kg, P<0.001, 10-15 min), it has a short duration of action (˜15 min). THP Sal A attenuated both thermal and inflammatory pain. Unfortunately, it was also sedative at both 1 mg/kg (P<0.01, 15-45 min) and 2 mg/kg (P<0.001, 15-90 min). Mesyl Sal B significantly attenuated both central (1mg/kg, P<0.01, 30-60 min) and peripheral (2 mg/kg, P<0.01, 30 min) pain processes. Although Mesyl Sal B was found to have a weak analgesic effect in all pain assays, it was not sedative. Conclusions and Implications: KOPr agonists attenuate acute nociceptive and inflammatory pain. Structural modification of Sal A at the C-2 position alters its analgesic effects in vivo. Substitution with a tetrahydropyran group greatly improves central analgesic effects; however, sedative effects were also observed. Although substitution with a mesylate group produced no sedative effects, it had reduced effects on central and peripheral pain processes. The lack of sedation by Mesyl Sal B makes it a good target for future research in pain. Its longer duration of action compared to Sal A suggests it has a better metabolic profile. The creation of more soluble KOPr compounds would allow for better dose-testing to evaluate therapeutic potential of KOPr analgesics.</p>

Kappa Opioid Receptor Agonists: New Targets In The Treatment Of Pain

<p>Background and Purpose: Pain, although necessary for survival, can become pathological affecting an estimated 1 in 5 adults globally. It is also the most common reason people seek medical attention. Mu opioid receptor (MOPr) agonists, such as morphine, are the gold standard treatment for pain. Although these drugs have excellent analgesic properties, adverse effects such as addiction, tolerance and respiratory depression make their use problematic. An estimated 10,000 New Zealanders are addicted to prescription opiates, highlighting the need for better drugs to treat pain. Kappa opioid receptor (KOPr) agonists have analgesic properties and, unlike MOPr agonists, are also anti-addictive. Unfortunately, adverse effects such as sedation and dysphoria, have limited their therapeutic potential. The discovery of KOPr agonists that have analgesic properties without inducing adverse effects can allow for better, more efficient treatments of pain. We are the first to report the analgesic potential of novel Salvinorin A (Sal A) analogues: Tetrahydropyran Salvinorin A (THP Sal A) and Mesyl Salvinorin B (Mesyl Sal B). Experimental Approach and Compounds Tested: This study uses animal behavioural models to characterise the analgesic, anti-oedematous, sedative and hypothermic effects of a structurally new class of KOPr agonists including Sal A, THP Sal A and Mesyl Sal B. The known peripherally restricted KOPr agonist, ICI 204,448, was used to evaluate the peripherally mediated analgesic mechanisms of KOPr agonists. The tail-flick and intradermal formalin test were used to assess acute central and peripheral pain processes respectively. Sedative effects were monitored via rotarod performance test; thermoregulatory effects were also recorded. Key Results: ICI 204,448 attenuated inflammatory pain at a dose of 1 mg/kg (P<0.05, 30 min) and 2 mg/kg (P<0.001, 30-35 min). Although it showed no centrally mediated analgesic effects, it was found to be sedative at a dose of 2 mg/kg (P<0.01, 15-60 min). Sal A (2 mg/kg) attenuated inflammatory pain (P<0.01, 25-35 min) at the same dose it was sedative (P<0.01, 2-15 min). Although it treated acute thermal pain at a non-sedative dose (1 mg/kg, P<0.001, 10-15 min), it has a short duration of action (˜15 min). THP Sal A attenuated both thermal and inflammatory pain. Unfortunately, it was also sedative at both 1 mg/kg (P<0.01, 15-45 min) and 2 mg/kg (P<0.001, 15-90 min). Mesyl Sal B significantly attenuated both central (1mg/kg, P<0.01, 30-60 min) and peripheral (2 mg/kg, P<0.01, 30 min) pain processes. Although Mesyl Sal B was found to have a weak analgesic effect in all pain assays, it was not sedative. Conclusions and Implications: KOPr agonists attenuate acute nociceptive and inflammatory pain. Structural modification of Sal A at the C-2 position alters its analgesic effects in vivo. Substitution with a tetrahydropyran group greatly improves central analgesic effects; however, sedative effects were also observed. Although substitution with a mesylate group produced no sedative effects, it had reduced effects on central and peripheral pain processes. The lack of sedation by Mesyl Sal B makes it a good target for future research in pain. Its longer duration of action compared to Sal A suggests it has a better metabolic profile. The creation of more soluble KOPr compounds would allow for better dose-testing to evaluate therapeutic potential of KOPr analgesics.</p>

Shoulder Pain — Where Are We Now?

Purpose of Review Shoulder pain is common and costly. For the past century, diagnosis and management has been based upon presumed patho-anatomical abnormalities. With the evolution of imaging techniques and new insight about the causes of musculoskeletal pain, this review evaluates the evidence that a patho-anatomical approach remains justified. Recent Findings Imaging modalities have developed considerably but, so far, have only proven value in evaluating full thickness rotator cuff tears prior to surgery. Correlation between imaging findings and symptoms is otherwise poor, with limited evidence of the value and impact of imaging for decision-making. Much of shoulder pain is chronic and few people have single-site musculoskeletal pain. Pain studies suggest that chronic shoulder pain is associated with both central and peripheral pain sensitisation. Moreover, functional MRI points to an effect of cognitive affective pain processing rather than nociception. Few of the established therapies, medical or surgical, that treat the presumed patho-anatomical cause have been shown to have lasting benefit. Summary Much of the evidence suggests that shoulder pain is more similar than different from mechanical low back pain. For most people with shoulder pain, the best approach might well be de-medicalisation, support to (self)manage pain, emphasis on retaining movement and identifying adverse beliefs and risk factors for disability and chronicity. Approaches like this are currently being evaluated and more research is desperately required.

Pathophysiology of pain in cancer and other terminal illnesses

Cancer pain involves a myriad of peripheral changes in the function of tissues and nerves, at the site of the tumour growth, as well as a number of consequent changes in the processing of pain messages at the spinal cord level with implications for the pain experience at higher centres. This chapter reviews the changes in peripheral pain signalling, notes the likely prevalence of both inflammatory and neuropathic components, and describes the altered events at spinal levels and within the circuits of pain in higher brain areas that can help explain the ongoing pain, hyperalgesia, and allodynia that patients with cancer and other chronic illnesses, such as HIV/AIDs, experience. The mechanisms of action of therapies, both existing and potential novel approaches, are also described. The importance of these processes in the development and treatment of chronic pain is an emerging issue, particularly as the problem of persistent pain in cancer survivors increases in prevalence.

Macrophage as a Peripheral Pain Regulator

A neuroimmune crosstalk is involved in somatic and visceral pathological pain including inflammatory and neuropathic components. Apart from microglia essential for spinal and supraspinal pain processing, the interaction of bone marrow-derived infiltrating macrophages and/or tissue-resident macrophages with the primary afferent neurons regulates pain signals in the peripheral tissue. Recent studies have uncovered previously unknown characteristics of tissue-resident macrophages, such as their origins and association with regulation of pain signals. Peripheral nerve macrophages and intestinal resident macrophages, in addition to adult monocyte-derived infiltrating macrophages, secrete a variety of mediators, such as tumor necrosis factor-α, interleukin (IL)-1β, IL-6, high mobility group box 1 and bone morphogenic protein 2 (BMP2), that regulate the excitability of the primary afferents. Neuron-derived mediators including neuropeptides, ATP and macrophage-colony stimulating factor regulate the activity or polarization of diverse macrophages. Thus, macrophages have multitasks in homeostatic conditions and participate in somatic and visceral pathological pain by interacting with neurons.

Principles of choosing an analgesic depending on the intensity of pain

Pain is one of the most common symptoms in modern clinical practice and one of the most frequent causes for patients to seek medical attention. Nonsteroidal anti-inflammatory drugs have traditionally been the leading means of protecting peripheral pain receptors. However, taking nonsteroidal anti-inflammatory drugs is associated with a range of complications. This review analyzes current studies of dexketoprofen that demonstrate its safety and clinical effect for the treatment of pain syndrome.

AB0510 THE ROLE OF BONE SCINTIGRAPHY FOR THE FOLLOW-UP EVALUATION OF INFLAMMATORY ACTIVITY IN PATIENTS WITH SERONEGATIVE SPONDYLOARTHRITIS

Background:The use of bone scintigraphy (Sc) in spondyloarthritis (SpA) as a technique for diagnosis, assessment of activity and treatment decision has been questioned by the scientific community. Due to its low cost compared to Magnetic Resonance Imaging - MRI (the gold standard)1, some studies proposed to evaluate Sc’s diagnostic accuracy. These studies have shown that Sc has a low diagnostic sensitivity of 50-55%2. Also, there is a poor correlation between symptoms and scintigraphic uptake3. We aimed to evaluate the use of Sc for management and follow-up of patients with SpA.Objectives:To determine if Sc activity correlates with patients’ complaints (peripheral and axial), inflammatory markers, disease activity scores and whether it influenced physicians’ treatment decisions during the follow-up of the disease.Methods:We performed a retrospective review of all patients at our department with SpA with at least one Sc from 2018 to 2020. The following variables were analyzed: demographic data, spondyloarthropathy subtype (ankylosing, enteropathic, psoriatic and undifferentiated SpA), axial or peripheral pain, Sc findings (inflammatory vs no-inflammatory activity), inflammatory markers (sedimentation rate - ESR and C-Reactive Protein - CRP), disease activity scores within one year since the Sc (Ankylosing Spondylitis Disease Activity Score with Erythrocyte Sedimentation Rate - ASDAS-ESR and Bath Ankylosing Spondylitis Disease Activity Index - BASDAI) and treatment at the time of the Sc (non-steroidal anti-inflammatory drugs, conventional synthetic disease-modifying antirheumatic drugs (DMARDs), target synthetic DMARDs and biologic DMARD. Treatment decisions (escalation, de-escalation or maintenance) in accordance to Sc results were also reviewed.We used the non-parametric Mann-Whitney’s U test for comparisons between ordinal or numerical variables. For correlations between categorical variables we used the Fisher’s exact test and the χ2-independence test. Tests with p < 0.05 were statistically significant.Results:Fifty-five patients were reviewed, 75% women; median age of 48 years. Seventy-one percent had ankylosing SpA, 15% enteropathic SpA, 5% psoriatic SpA, 5% undifferentiated and 4% reactive SpA. Sixty-two percent of the patients had both axial and peripheral pain and 24% only axial complaints. Sixty-two percent of the patients had a Sc with no inflammatory changes, 27% had peripheral and 25% had axial inflammatory changes; 15% had evidence of both peripheral and axial inflammation. For ankylosing SpA, the median ASDAS-ESR was 2.89 and according to the BASDAI, 66% had active disease. The median CRP and ESR in patients with inflammatory vs a normal Sc was not different (p=0.02 vs p=0.36, respectively). Similarly, Sc findings were not correlated with patients’ axial (p=0.10) or peripheral pain (p=1.0), neither with the ASDAS-ESR (p=0.29) or the BASDAI (p=0.29). There was no correlation between inflammatory activity in Sc and the decision to maintain, escalate or de-escalate treatment (p=0.65), including the decision to start a biological DMARD (p=1.0) or to switch between biological DMARDs (p=0.19).Conclusion:There was no correlation between Sc findings and ESR, patients’ complaints, disease activity or treatment decisions. Considering previous research showing a low diagnostic sensitivity, our findings seem to support a limited role of bone Sc for the follow-up and management of patients with seronegative SpA.References:[1]Khmelinskii N, Regel A, Baraliakos X. The Role of Imaging in Diagnosing Axial Spondyloarthritis. Front Med. 2018;5. doi:10.3389/fmed.2018.00106[2]Poddubnyy D. Classification vs diagnostic criteria: the challenge of diagnosing axial spondyloarthritis. Rheumatology. 2020;59(Supplement_4):iv6-iv17. doi:10.1093/rheumatology/keaa250[3]Shim JS, Kim C, Ryu JJ, Choi SJ. Correlation between TM joint disease and rheumatic diseases detected on bone scintigraphy and clinical factors. Sci Rep. 2020;10(1):4547. doi:10.1038/s41598-020-60804-xDisclosure of Interests:None declared.

Oxaliplatin Causes Transient Changes in TRPM8 Channel Activity

Oxaliplatin is a third-generation platinum-based anticancer drug that is widely used as first-line treatment for colorectal carcinoma. Patients treated with oxaliplatin develop an acute peripheral pain several hours after treatment, mostly characterized by cold allodynia as well as a long-term chronic neuropathy. These two phenomena seem to be causally connected. However, the underlying mechanisms that trigger the acute peripheral pain are still poorly understood. Here we show that the activity of the transient receptor potential melastatin 8 (TRPM8) channel but not the activity of any other member of the TRP channel family is transiently increased 1 h after oxaliplatin treatment and decreased 24 h after oxaliplatin treatment. Mechanistically, this is connected with activation of the phospholipase C (PLC) pathway and depletion of phosphatidylinositol 4,5-bisphosphate (PIP2) after oxaliplatin treatment. Inhibition of the PLC pathway can reverse the decreased TRPM8 activity as well as the decreased PIP2-concentrations after oxaliplatin treatment. In summary, these results point out transient changes in TRPM8 activity early after oxaliplatin treatment and a later occurring TRPM8 channel desensitization in primary sensory neurons. These mechanisms may explain the transient cold allodynia after oxaliplatin treatment and highlight an important role of TRPM8 in oxaliplatin-induced acute and neuropathic pain.