Pain

• Chronic pain affects 30% of people worldwide
• Arthritis is the leading cause of this chronic pain
• Around 15.5 million people in England (34% of the population) have chronic pain
• Arthritis is the leading cause of this chronic pain in England
• Musculoskeletal conditions such as arthritis, are the commonest cause of chronic pain
• There are barriers to pain care, including disproportionate access to and use of established pain treatments, inadequate pain education, inappropriate diagnosis and undertreatment
• There are pain inequities between high-income countries and low- and middle-income countries, as well as within countries based on factors such as race, sex, gender, ethnicity, socioeconomic status, and age
• Chronic pain is more prevalent in women than men. Women (14%) report more severe pain than men (9%)
• Chronic pain disproportionately affects some minority ethnic groups. Black people are more likely to have chronic pain than people of other ethnic backgrounds
• There has been a rise in chronic pain in young adults, from 21% to 32% between 2011 and 2017
• People who experience severe chronic pain are twice as likely to live in the most deprived areas (30%) compared to the least deprived areas (15%)
• Pain


  An unpleasant sensory and emotional experience associated with, or resembling that which is associated with, actual or potential tissue damage
• Acute pain


  Pain lasting up to 3 months in duration from onset
• Chronic pain


  Pain lasting for 3 months or more from onset
• Chronic pain is a multi-dimensional and subjective experience, generated by biological changes, interconnected with psychological and social factors, and perpetuates beyond the resolution of noxious stimuli
• Chronic pain arises from a combination of


  • Nociceptive changes: from tissue injury
  • Neuropathic changes: from nerve injury
  • Nociplastic changes: sensitisation; dysfunctional pain processing in absence of tissue or nerve damage
• The treatment approach for chronic pain should ideally be a personalised multimodal, interdisciplinary treatment approach, which may include pharmacotherapy, psychotherapy and integrative treatments
• Osteoarthritis


  An age-related degenerative condition that mainly affects large weight-bearing synovial joints
• Normal joint


  • Smooth cartilage overlying the tibia and femur (avascular & aneural)
  • Tibia and femur (subchondral bone) contain osteoclasts, osteoblasts, osteocytes, nerves, blood vessels, bone-marrow containing immune cells
  • Synovium maintains the synovial fluid which lubricates the joint
  • Meniscus acts as a shock absorber
• Osteoarthritis joint


  • All joint tissues including synovium, cartilage, bone and meniscus are affected
  • Protective cartilage breaks down, exposing underlying bone
  • Abnormal bone formation (osteophytes)
  • Meniscal and ligament tears/damage
  • Leads to inflamed, painful and damaged joints, causing disability
• Pain in osteoarthritis can be intermittent, flares, dull/sharp, mild to moderate to severe, and worsen on movement
• The feeling of pain, severity of joint damage and intensity of inflammation varies in people living with arthritis
• Chronic pain components in osteoarthritis


  • Nociceptive
  • Inflammatory
  • Neuropathic
• Initiation of chronic pain in osteoarthritis


  1. Cartilage and bone damage release inflammatory mediators

  2. Synovium gets inflamed (synovitis)

  3. Inflammatory cascade leads to accumulation of plasma proteins, white blood cell aggregation, mast cell degranulation, platelet activation, vasodilation and angiogenesis
• Nociceptors


  Primary sensory afferent neurons detecting noxious stimuli
• The knee joint is innervated by sensory peripheral nerve fibres, sympathetic peripheral nerve fibres, and performs actions such as nociception, vasoregulation and proprioception
• Hyperalgesia


  Increased sensitivity to a painful stimulus
• Allodynia


  Pain due to a stimulus that does not normally provoke pain
• Neurogenic inflammation following joint injury/damage triggers the release of neuropeptides and neurotransmitters, causing vasodilation, leukocyte infiltration, mast cell degranulation, and microglia/astrocyte activation, leading to increased production of proinflammatory mediators and cytokines
• Central sensitisation in chronic joint pain


  1. Continuous neuronal firing from damaged joint nociceptors lowers threshold of spinothalamic neurons in dorsal horn of the spinal cord

  2. This leads to hyperexcitability through activation or modulation of membrane channels/receptors, release of pro-nociceptive and pro-inflammatory factors from microglia and astrocytes, and loss of local inhibitory regulation
• Pain Pathway


  1. Transduction

  2. Transmission

  3. Perception

  4. Modulation
• Central Sensitisation

  Chronic joint pain is not purely dictated by changes in the joint (peripheral changes/sensitisation), it is also governed by nociceptive processing in the spinal cord and brain
• Central Sensitisation


  1. Continuous neuronal firing from the damaged knee joint nociceptors (first order neurons) lowering threshold of spinothalamic neurons in dorsal horn of the spinal cord (second order neurons)

  2. Activation or modulation of membrane channels or receptors (ion channels)

  3. Release of pro-nociceptive and pro-inflammatory factors from microglia and astrocytes (interleukins)

  4. Loss of local inhibitory regulation
• Central Sensitisation


  • Neuron, Astrocytes, Microglia
• Central Sensitisation - Pain perception and Modulation


  1. Excessive nociceptive ascending signals (third order neurons) to the cortex

  2. Cortex helps to identify how much the joint hurts and the location of the pain

  3. Deficient inhibitory descending signals (opioid, GABA) via inhibitory interneurons (enkephalins, endorphins, dynorphins) into dorsal horn of spinal cord
• Hyperalgesia


  Increased sensitivity to noxious stimuli
• Allodynia


  Pain in response to normally innocuous stimuli
• Referred Pain


  Larger area of pain receptive field and longer duration of pain
• Neuropathic Pain


  Pain associated with permanent nerve damage
• Studies show there is a discordance between pain severity and the degree of joint damage