Pain Educational Materials

Pain    A sensation associated with actual or perceived damage to tissue. Usually induced by activation of nociceptors in the periphery, but can be established anywhere along the sensory pathway. There are two different types of axons that mediate different types of pain: o Thinly myelinated (group III afferents, Aδ fibres) mediate fast pain (e.g. prick). o Unmyelinated (group IV afferents, C fibres) mediate slow pain (e.g. burning). Blocking axons  Pressure/ischaemia – inflation of a sphygmomanometer cuff around upper arm. o The susceptibility of axons to pressure/ischaemia block depends on diameter. o Large axons are more susceptible because of their greater energy requirements. o Block afferent input from groups I – II afferents abolishes discriminative touch and proprioceptive inputs. o Block skeletomotor axons (α-motoneurones) leads to muscular paralysis. o Block of group III afferents (Aδ) abolishes perception of cold stimuli and fast (pin prick) pain. Cold now feels warm because they can act on C fibres. o Block of group IV (C) afferents abolishes perceptions of hot stimuli and slow (burning) pain. o Blocking the C fibres takes about 40 minutes.  Local anaesthetic. o Preferentially blocks unmyelinated axons first, working its way up. o Therefore, opposite effect to pressure/ischaemia. Gate    control theory Proposed by Melzac and Wall (1968). Stimulation of large-diameter myelinated afferents can inhibit pain. Believe to occur through presynaptic inhibition within the superficial laminae of the dorsal horn. Terminology of pain  Hyperalgesia: increased sensitivity to pain, brought about through peripheral or central mechanisms.  Hypoalgesia: decreased sensitivity to pain.  Allodynia: pain produced by a non-noxious stimulus (e.g. light stroking). Phantom limb pain    Pain perceived in an amputated limb, initially produced by nerve irritation at the neuroma (which forms over the end of the cut nerve). Can be maintained by central processes; reorganisation of the primary somatosensory cortex occurs with expansion of normally innervated areas (e.g. face) into the denerved area (e.g. hand). In some amputees, stroking the face can induce sensations (including pain) that the subject perceives to originate in the amputated hand. Quality of pain  The quality of pain depends on the tissue from which it originates.  Although pain follows the path of the anterolateral tract, there are differences in the quality of pain.  Pain originating in the skin is perceived as sharp and/or burning. o Localisation of the source is good, comparable to the tactile acuity of non-noxious punctate stimuli.  Pain originating in muscle is perceived as a deep, dull ache. o Localisation of the source is poor; the pain is diffuse and often refers into distal structures.  Experimental pain model in human subjects: o Subcutaneous injection of hypertonic saline (5%, 0.2mL) is easily localised compared to intramuscular injection of hypertonic saline (5%, 0.5mL), which is more diffuse. o Subjects rate pain intensity using visual analogue scale (VAS) from 0 to 10. o Subjects rate pain quality using McGill Pain Questionnaire. Processing pain in the brain  fMRI was used to assess whether there were differential cortical and subcortical processing of deep, muscular pain and superficial, cutaneous pain.  Deep (intramuscular) and superficial (cutaneous) pain cause increases in signal intensity in the anterior mid-cingulate and posterior mid-cingulate cortex.  Deep, but not superficial, pain increases in signal intensity in the cingulate motor area and the ipsilateral (right) anterior insular cortex. o Electrical stimulation of the right anterior cingulate cortex in human subjects has shown to increase BP. o Patients with lesions involving the anterior cingulate cortex do not generate cardiovascular arousals during cognitive tests.  There is a somatotopic representation of pain within the posterior insula, suggesting that it may be involved in stimulus localisation. o Patients report pain when the insula is electrically stimulated, but do not when the primary somatosensory cortex is stimulated. o Painful quality of noxious inputs do not reside in the somatosensory cortex, but rather in the insula (i.e. primary  somatosensory cortex knows where stimulus is coming from, but has no idea if it is noxious). Deep, but not superficial, pain decreases in signal intensity in the perigenual cingulate cortex. o The perigenual cingulate is linked to the affective content of pain. o Chronic deep pain often causes negative emotion (depression); activity is low in patients with depression. o Deep brain stimulation within the perigenual cingulate cortex can alleviate depression. Integration of the pain circuit  It has been suggested that the anterior cingulate cortex (ACC) evolved first as a motor-control region, aligned with sensory integration of olfactory-guided (smell) group behaviour.  The insula evolved later for cortical processing of homeostatic sensory activity.  The ACC and insula became linked for integrative autonomic control, and in mammalian evolution, the insula grew as behavioural activity became aligned more with autonomic activity, than with olfactory activity. Difference between males and females  Pain activates pain neuromatrix (cingulate insula and somatosensory cortices) and evoke gender-specific differences in the: o Mid cingulate cortex. o Prefrontal cortex. o Hippocampus (no change in activity in males; goes down in females). o Posterior thalamus (no change in activity in males; goes down in females). o Cerebellar cortex (activity goes up in males; no change in females).  May underlie gender bias that exists in some chronic pain conditions. Chronic pain  Characterised by pain that has lasted >3 months.  Incidence of chronic pain after nerve injury: o >50% of patients following limb amputation. o Around 50% of women following a mastectomy o Around 50% of patients with intercostal nerve dysfunction following a thoracotomy. o Following elective surgery, over 27% of patients develop chronic pain of high intensity; in over 20% of patients, there was moderate or severe limitation to work and other activities. Types of chronic pain    Nociceptive pain: produced by activation of group III and IV nociceptor afferents in the periphery. Peripheral neuropathic pain: established by damage or irritation of peripheral or cranial nerves. Central neuropathic pain: sustained by changes in the CNS. o Once the abnormal central pattern generating processes are underway, the peripheral contributes may assume less importance. o Transecting the spinal cord offered no relief of pain. Chronic pain states  Sensory changes: hyperalgesia and allodynia.  Unremitting pain and complaint.  Disturbance of family and social relationships.  Disturbance of sleep pattern.  Loss of interest and attention to outside activities.  Restriction of movement (quiescence).  Loss of appetite.  Loss of libido.  Disturbance of menstrual periods. Clinical correlation: chronic orofacial pain  Two forms of chronic pain: o Nociceptive pain: temperomandibular joint disorder (TMD). o Neuropathic pain: trigeminal neuropathic pain (TN).  Central anatomical changes occurred in patients with TN, but not in those with TMD.  In TN, there is significant cell loss in the thalamus, nucleus accumbens, putamen, and primary somatosensory cortex. o Level of pain was directly related to cell loss in the contralateral thalamus. Clinical correlation: spinal cord injury  Central reorganisation of the primary somatosensory cortex occurs following spinal cord injury. o Changes in the somatotopic representation on the cortex of each stimulated body part can be measured relative to an anatomical landmark. o Reorganisation is greater in patients with below-level neuropathic pain.  There is significant correlation between pain intensity and the degree of cortical reorganisation following SCI.  Subjects with greater reoorganisation report more neuropathic pain below lesion.  Loss of neurones within the ventroposterior thalamus occurs in patients with complete spinal cord injury; greater loss is related to most pain.  There seems to be an increase in neural activity in primary motor cortex in patients.   Both patients and controls have increased activity in supplementary motor area during movement imagery. Increases in ongoing pain during imagination are associated with increased neural activity in anterior insula, dorsolateral prefrontal cortex, premotor cortex and supplementary motor area. Conclusion  Pain is a sensation associated with actual or perceived damage to tissue, usually induced by activation of nociceptors in the periphery, but can be established anywhere along the sensory pathway – such as the thalamus.  Thinly myelinated (group III afferents, Aδ fibres) axons mediate fast pain (e.g. pin prick).  Unmyelinated (group IV afferents, C fibres) axons mediate slow pain (e.g. burning).  The pain neuromatrix includes the ventroposterior nucleus of the thalamus, cingulate cortex, insula and primary and secondary somatosensory cortices.  Gender-specific changes in neural activity also occur in the midcingulate cortex, prefrontal cortex, hippocampus and cerebellar cortex.  There are differences in the cortical and subcortical sites engaged in the processing of pain originating in muscle and skin.  There are differences in the cortical and subcortical processing of pain in males and females.  There is a somatotopic representation of pain within the dorsal posterior insula.  Chronic pain is usually established by peripheral (nociceptive) inputs, but can be maintained by central processes.  Neuropathic – but not nociceptive – chronic pain is associated with changes in brain anatomy.  In chronic trigeminal neuropathic pain, loss of neurones in the thalamus is associated with decreases in blood flow to the thalamus.  These thalamic changes may underlie changes in neural activity of the entire pain neurotmatrix.  In patients with trigeminal neuropathic pain, there is significant cell loss in the ventroposterior thalamus, nucleus accumbens, putamen and primary somatosensory cortex.  In patients with complete spinal cord injury, there is loss of neurones within the ventroposterior thalamus; this is higher in those with below-level neuropathic pain, and the neuronal loss is greater in those with the most pain.  Neuropathic pain associated with spinal cord injury leads to reorganisation of the primary somatosensory cortex, and the pain increases during imagined movements of the legs.