Pathophysiology

Nociceptive pain typically originates from tissue damage caused by trauma, non-healing injury or inflammatory processes, and can be divided into two categories: somatic pain (injuries of the musculoskeletal system) and visceral pain (internal organ injury, often felt indirectly).^1,3,5 In response to actual or potentially harmful chemical, mechanical or thermal stimuli, the two types of primary afferent nociceptors, Aδ- and C-fibres, transmit nerve signals to the dorsal horn of the spinal cord and ascending cortical pathways to the brain.¹ If a noxious stimulus exceeds the threshold for tissue damage, peripheral sensitivity to subsequent stimuli increases.¹ While sensitisation is only temporary if subsequent stimuli are short in duration, the continuous presence of stimuli and resulting sensitisation may lead to changes to the peripheral nerves and central nervous system (CNS).¹

Neuropathic pain is classically caused by lesions within, or diseases that affect, the somatosensory nervous system.¹ Another cause of neuropathic pain is injury or trauma during surgery.¹ Following nerve injury or damage, disordered neural processing in the peripheral or central nervous system, as well as cell death, may occur.¹ Such changes can lead to abnormal pain sensations.¹

Also known as central sensitisation, sensory hypersensitivity or central hypersensitivity, nociplastic pain manifests as the perception of pain despite no clear evidence of actual or threatened tissue damage causing the activation of peripheral nociceptors, nor evidence for disease of or lesion of the somatosensory system causing the pain.^1,3 Nociplastic pain describes the increased responsiveness of nociceptive neurons in the periphery and CNS to their normal and subthreshold afferent input, resulting in increased sensitivity such that stimuli that would be deemed non-harmful under normal conditions now trigger a pain response.^5,6 This phenomenon is driven by hundreds of molecular changes.¹