Chronic Pain After Surgery
Chronic Pain After Surgery
The trauma and inflammation that occurs from cutting and handling tissues during surgery activates nociceptors. Nociceptive stimuli are transduced into electrical impulses that are carried to the spinal cord via primary afferent Aδ and C fibres. Primary afferent neurones synapse with secondary afferent neurones in the dorsal horn of the spinal cord and carry impulses to higher centres via the contralateral spinothalamic and spinoreticular pathways, the two main ascending pain pathways. There are multiple further projections to the cerebral cortex and other higher centres. Central processing of impulses leads to the experience of pain. The complex pathways of nociceptive transmission are well described (figure 1).
(Enlarge Image)
Figure 1.
Ascending pain pathways reproduced with permission. DRG, dorsal root ganglion; PAG, periaqueductal grey matter.
Inflammatory pain occurs because sensitising, inflammatory mediators including cytokines, bradykinin and prostaglandins are released from injured and inflammatory cells at the site of tissue damage. Nociceptors demonstrate reversible plasticity in response to inflammatory mediators. The activation threshold of nociceptors is lowered, resulting in enhanced pain sensitivity at the site of tissue injury (peripheral sensitisation). Non-steroidal anti-inflammatory drugs inhibit the production of prostaglandin E2 via locally induced cyclooxygenase-2 enzymes and hence reduce peripheral sensitisation and pain. This type of inflammatory pain, secondary to local excitability, usually subsides once the source of the mediators subsides, as tissue healing occurs or the disease process is controlled. Heightened pain sensitivity can contribute to healing by helping to protect the damaged body part until repair has occurred.
The central nervous system also demonstrates plasticity in response to pain, and pain signalling within the spinal cord can be enhanced. With ongoing nociceptive input, the stimulus–response relationship is altered and an increase in excitability of neurones in the central nervous system may occur, known as central sensitisation. Clinically this manifests as an increased response to painful stimuli (hyperalgesia), and pain secondary to normally non-painful tactile stimuli (allodynia).
Wind-up, long-term potentiation and secondary hyperalgesia are all processes associated with central sensitisation. Wind-up occurs with repeated activation of C fibres and is due to the action of glutamate at NMDA (N-methyl-D-aspartate) receptors. Under normal conditions, a magnesium ion blocks the NMDA receptor. With ongoing painful stimuli, the magnesium block is removed and the response of second-order neurones to painful stimuli is amplified. This explains why NMDA receptor antagonists, such as ketamine, are useful in attenuating or blocking wind-up. The response of second-order neurones may outlast the initial stimulus and this is known as long-term potentiation, contributing to hyperalgesia. A lowering of the pain threshold outside of the area of inflammation (secondary hyperalgesia) occurs because of increased activation of second-order neurones in the dorsal horn of the spinal cord.
Nerve damage plays a role in CPSP. Following nerve injury, spontaneous ectopic discharges from injured nerves and nearby uninjured nerves lead to spontaneous pain. The increased nociceptive input in to the dorsal horn contributes to central sensitisation. A loss of inhibitory interneurons in the dorsal horn results in a disinhibition of pain pathways and facilitation of pain transmission.
The process of central sensitisation is thought to be important for the development of persistent pain; hence, surgical techniques and pharmacological interventions to minimise central sensitisation are of great interest.
Pathophysiology
The trauma and inflammation that occurs from cutting and handling tissues during surgery activates nociceptors. Nociceptive stimuli are transduced into electrical impulses that are carried to the spinal cord via primary afferent Aδ and C fibres. Primary afferent neurones synapse with secondary afferent neurones in the dorsal horn of the spinal cord and carry impulses to higher centres via the contralateral spinothalamic and spinoreticular pathways, the two main ascending pain pathways. There are multiple further projections to the cerebral cortex and other higher centres. Central processing of impulses leads to the experience of pain. The complex pathways of nociceptive transmission are well described (figure 1).
(Enlarge Image)
Figure 1.
Ascending pain pathways reproduced with permission. DRG, dorsal root ganglion; PAG, periaqueductal grey matter.
Inflammatory pain occurs because sensitising, inflammatory mediators including cytokines, bradykinin and prostaglandins are released from injured and inflammatory cells at the site of tissue damage. Nociceptors demonstrate reversible plasticity in response to inflammatory mediators. The activation threshold of nociceptors is lowered, resulting in enhanced pain sensitivity at the site of tissue injury (peripheral sensitisation). Non-steroidal anti-inflammatory drugs inhibit the production of prostaglandin E2 via locally induced cyclooxygenase-2 enzymes and hence reduce peripheral sensitisation and pain. This type of inflammatory pain, secondary to local excitability, usually subsides once the source of the mediators subsides, as tissue healing occurs or the disease process is controlled. Heightened pain sensitivity can contribute to healing by helping to protect the damaged body part until repair has occurred.
The central nervous system also demonstrates plasticity in response to pain, and pain signalling within the spinal cord can be enhanced. With ongoing nociceptive input, the stimulus–response relationship is altered and an increase in excitability of neurones in the central nervous system may occur, known as central sensitisation. Clinically this manifests as an increased response to painful stimuli (hyperalgesia), and pain secondary to normally non-painful tactile stimuli (allodynia).
Wind-up, long-term potentiation and secondary hyperalgesia are all processes associated with central sensitisation. Wind-up occurs with repeated activation of C fibres and is due to the action of glutamate at NMDA (N-methyl-D-aspartate) receptors. Under normal conditions, a magnesium ion blocks the NMDA receptor. With ongoing painful stimuli, the magnesium block is removed and the response of second-order neurones to painful stimuli is amplified. This explains why NMDA receptor antagonists, such as ketamine, are useful in attenuating or blocking wind-up. The response of second-order neurones may outlast the initial stimulus and this is known as long-term potentiation, contributing to hyperalgesia. A lowering of the pain threshold outside of the area of inflammation (secondary hyperalgesia) occurs because of increased activation of second-order neurones in the dorsal horn of the spinal cord.
Nerve damage plays a role in CPSP. Following nerve injury, spontaneous ectopic discharges from injured nerves and nearby uninjured nerves lead to spontaneous pain. The increased nociceptive input in to the dorsal horn contributes to central sensitisation. A loss of inhibitory interneurons in the dorsal horn results in a disinhibition of pain pathways and facilitation of pain transmission.
The process of central sensitisation is thought to be important for the development of persistent pain; hence, surgical techniques and pharmacological interventions to minimise central sensitisation are of great interest.
