ICRS 2019 - Conference Calendar

Displaying One Session

Georgia Special Session
Session Type
Special Session
Date
06.10.2019
Time
15:15 - 16:15
Location
Georgia
Extended Abstract (for invited Faculty only) Osteoarthritis

11.3.1 - Pain - Where is it Coming From?

Presentation Number
11.3.1
Presentation Topic
Osteoarthritis
Lecture Time
15:15 - 15:35
Session Name
Session Type
Special Session
Corresponding Author

Abstract

Introduction

What is joint pain?

Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage (1). Pain is both sensory and emotional; if we enjoyed pain, it might not be a medical problem! Self-reported pain severity reflects both sensory and emotional components. Pain that is expected, understood to be part of a healing process, and known to be temporary, for example shortly after joint replacement surgery, may be rated as less severe, than is pain which is unexpected, thought to indicate ongoing damage and thought to be permanent or that will deteriorate. Nociception is the body’s detection of damage, and results in pain. However, pain is not always nociceptive. Fibromyalgia pain can occur in the absence of articular pathology, even when experienced in response to mechanical stimulation from weight-bearing or walking. Pain experienced during normal activity results from neuronal sensitisation, an increased responsiveness of neurones in the sensory pathways to a standard input. Peripheral sensitisation occurs when there is an increased activity in primary afferents, for example during normal joint movement or loading. Central sensitisation occurs when a standard afferent input results in higher activity along neuronal pathways of the spinal cord or brain.

Joint pain is felt to originate from articular structures, due to its localisation or triggering by movement or pressure, for example within the knee or spine, from ligaments or muscles. Joint pain might be pain associated with musculoskeletal disease, although not all joint pain is indicative of joint pathology. Pain severity often displays only weak association with measures of underlying joint pathology. Radiographic knee OA is associated with knee pain, and predicts worse pain outcomes in people with knee pain, but even very severe radiographic OA is not always associated with pain. People often have multiple joint involvement, and multiple sites of pain that might vary from hour to hour during the day. Recognising the various underlying mechanisms that might mediate joint pain importantly informs appropriate treatment selection.

Content

The experience of joint pain

Joint pain is heterogeneous, and different pain experiences might indicate different pain mechanisms. Pain on weightbearing or movement that is intermittent (or intermittently more severe) suggests a biomechanical component. Constant pain suggests continual nociceptive input or activation of central pain pathways. Central sensitisation increases pain severity and spreading pain to sites not affected by pathology, including non-articular pain such as headache, abdominal and gynaecological pain. Central pain mechanisms interlink with other sensory, emotional and cognitive factors. Widespread pain, neuropathic-like symptoms, sleep disturbance, fatigue, anxiety, depressed mood, cognitive deficits (such as difficulty concentrating), or pain catastrophizing (interpretation of pain as necessarily indicative of harm or future problems) together constitute a single `central mechanisms’ trait, which is associated with knee pain severity, evidence from quantitative sensory testing of central sensitisation, and worse pain prognosis (2).

Burning or shooting pain qualities, or (rarely in musculoskeletal disease) pain on even light brushing of the skin or when touched by a cold object or water, each are characteristics of neuropathic pain. Neuropathic-like symptoms can be classified or measured using questionnaires (e.g. painDETECT, S-LANSS, DN4). Medical treatments effective for neuropathic pain (tricyclic antidepressants, gabapentinoids and selective serotonin and noradrenalin reuptake inhibitors (SSNRIs)) might also have benefit for neuropathic-like musculosketal pain, (3), even though actual pathology of the nervous system is rare in arthritis. Neuropathic-like musculoskeletal pain is associated with other evidence of central sensitisation, and also predicts poor pain outcomes following locally-directed treatments such as joint replacement surgery.

Sites of nociceptive drive

Injury-induced pain is normal, and people with congenital or acquired (e.g. diabetic neuropathy) pain insensitivity are at increased risk of joint pathology (Charcot’s joints). Joint pathology causes pain by activating normal articular nerves, by sensitising them to be activated by normal mechanical stimuli, exposing nerves to chemical or mechanical stimuli from which they would normally be protected, and by expanding articular innervation into otherwise aneural tissues that become sources of pain.

Sensory nerves are localised in the normal human knee to synovium, subchondral bone marrow spaces, ligaments, periosteum, outer one third of the meniscus, ligaments, tendons and muscles. It remains uncertain which of these nerves mediate pain. Associations of MRI OA structural changes suggest separate contributions from synovitis and subchondral bone, although correlation with cartilage and meniscal pathology suggest additional sites. Arthroplasty relieves OA pain even if synovitis persists, although intra-articular glucocorticoid injection can relieve OA pain without reversing structural pathology. Arthroplasty reduces biomechanical stresses in subchondral bone or surrounding tissues, and restores the physical barrier reducing flux of sensitising agents between the synovial cavity and subchondral bone. It removes articular cartilage which might itself be a source of sensitising factors such as NGF.

Sensory nerves within synovium and bone are fine, unmyelinated and peptidergic, containing neuropeptides substance P and calcitonin gene-related peptide (CGRP), and expressing the high affinity topomyosin receptor kinase A (TrkA) for nerve growth factor (NGF), ion channels such as transient receptor potential cation channel subfamily V member 1 (TrpV1) and the sodium ion channel Nav1.7. These slow conducting fibres transmit `burning’ or `aching’ pain. They often accompany blood vessels, although contributions of vascular pain in joints is less well established than that of CGRP in migraine. Ligaments, tendons and muscles in addition contain thinly myelinated sensory nerves that rapidly transmit from nociceptive mechanical stimuli.

Peripheral and central pain modulation

Nociceptors are silent during normal movement of the normal joint. Local inflammation activates and sensitises nerves within the joint. Consistently positive RCT results for NSAIDs in joint injury, osteoarthritis, back pain or inflammatory arthritis indicate contributions from cyclo-oxygenase products to joint pain. A key role for NGF has now also been established by clinical trials of antibodies which block NGF biological activity.

Pain severity and quality are strongly influenced by central sensitisation. Nociceptive inputs might be augmented, with recruitment of neuronal pathways mapping to regions away from the affected joint, and increased connectivity to brain regions involved in emotion (e.g. anterior cingulate gyrus, amygdala). Nociceptive transmission might alternatively be blunted within the CNS, with gating within the spinal cord, and descending inhibition from the brain and periaqueductal grey. The central augmentation/inhibition balance varies between individuals and with disease. Loss of central inhibitory control demonstrated by blunting of Conditioned Pain Modulation, or increased Temporal pain Summation is associated with more severe chronic pain, and predicts worse pain outcomes following treatment. Central inhibition contributes to placebo effects both of peripherally and centrally directed treatments. Benefits depend not only upon a surgical procedure, but also its psychosocial context.

To where does joint pain go?

Pain abolition is a strong motivating factor for patients and clinicians. Each pain mechanisms is a potential target for treatment, although all interventions have potential risks. Surgery might relieve or cause chronic pain, risking damage to peripheral nerves. Drugs can have off-target adverse effects. Understanding joint pain mechanisms should increase success rates from specific treatments by matching treatment to mechanism for the individual patient. Reducing nociceptive input can itself reduce central sensitisation. However, genetic, comorbid and psychosocial factors might provide barriers that need lifting to optimise analgesic response to peripherally targeted treatments.

References

1. https://en.wikipedia.org/wiki/International_Association_for_the_Study_of_Pain (accessed 31 July 2019)

2. Akin-Akinyosoye, K, Frowd, N, Marshall, L, Stocks, J, Fernandes, G, Valdes, A, McWilliams, DF, Zhang, W, Doherty, M, Ferguson, E, Walsh, DA. Traits associated with central pain augmentation in the Knee Pain in the Community (KPIC) cohort. Pain 2018, 159, 1035-44.

3. Sofat, N, Harrison, A, Russell, MD, Ayis, S, Kiely, PD, Baker, EH, Barrick, TR, Howe, FA. The effect of pregabalin or duloxetine on arthritis pain: a clinical and mechanistic study in people with hand osteoarthritis. J Pain Res. 2017; 10: 2437–2449.

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Extended Abstract (for invited Faculty only) Clinical Research

11.3.2 - How Pain Affects Outcomes

Presentation Number
11.3.2
Presentation Topic
Clinical Research
Lecture Time
15:35 - 15:55
Session Name
Session Type
Special Session
Corresponding Author
Extended Abstract (for invited Faculty only)

11.3.3 - Mechanisms of Joint Pain Reveal New Targets

Presentation Number
11.3.3
Lecture Time
15:55 - 16:15
Session Name
Session Type
Special Session
Corresponding Author