Neurosurgery notes/Functional/Pain

Pain

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Functional
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Pain definition
Persistent spinal pain syndrome
Trigeminal neuralgia
Complex regional pain syndrome (CRPS)
Chronic Pain
Phantom limb pain
Referred pain

General

  • The unpleasant sensory and emotional experience associated with actual or potential tissue damage
  • Forms of pain
    • Acute
      • Normal response to activation of nociceptors
    • Persistent pain
      • Common part of pathology resulting in consult
    • Chronic pain
      • No useful purpose
      • Always pathological

Types of pain

Pain types
Nociceptive
Neuropathic
Definition
Pain caused by physiological activation of pain receptors
Pain caused by lesion or dysfunction of the somatosensory system, especially the nociceptive pathway
Mechanism
Natural physiological transduction
Ectopic impulse generation, among others
Localization
Local + referred pain
Confined to innervation territory of the lesioned nervous structure
Quality of symptoms
Ordinary painful sensation (good verbal descriptors)
New strange sensations (poor verbal descriptors)
Treatment
Good response (conventional analgesics)
Poor-moderate response (antidepressants, antiepileptics)
  • Major types of pain:
    • “Sympathetically maintained” pain
      • The likes, e.g. causalgia
    • Dysfunctional/Functional
      • Pain without obvious organic cause.
    • Neuropathic pain
      • Pain caused by a lesion of the peripheral and/or central nervous system manifesting with sensory symptoms and signs
      • Deafferentation pain:
        • Deafferentation refers to the interruption or destruction of the afferent connections of nerve cells
        • Poorly localised.
        • Described as crushing, tearing, tingling or numbness.
          • Also causes burning dysesthesia numbness often with lancinating pain, and hyperpathia.
        • Unaffected by ablative procedures
      • Aetiological subtypes of neuropathic pain
          • Peripheral neuropathic pain
            • Acute & chronic inflammatory demyelinating polyradiculoneuropathy (CIDP)
            • Alcoholic polyneuropathy
            • Chemotherapy-induced polyneuropathy
            • Complex regional pain syndrome (CRPS)
            • Entrapment neuropathies
            • HIV sensory neuropathy
            • Iatrogenic neuralgias (e.g. postthoracotomy pain)
            • Idiopathic sensory neuropathy
            • Neoplastic nerve compression or infiltration
            • Nutritional-deficiency neuropathies
            • Painful diabetic neuropathy (PDN)
            • Phantom limb pain
            • Postherpetic neuralgia (PHN)
            • Postradiation plexopathy
            • Radiculopathy
            • Toxic exposure-related neuropathies
            • Trigeminal neuralgia
            • Posttraumatic neuralgias
          • Central neuropathic pain
            • Cervical spondylotic myelopathy
            • HIV myelopathy
            • Multiple sclerosis-related pain
            • Parkinson's disease-related pain
            • Postischemic myelopathy
            • Postradiation myelopathy
            • Poststroke pain
              • Thalamic stroke
            • Posttraumatic spinal cord injury pain
            • Syringomyelia
      • The only way to diagnose a true central pain syndrome is persistence of pain despite a complete motor and sensory blockade distal to the level of spinal or epidural anesthesia.
      • Medical treatment of neuropathic pain
        • No role of opioid for Neuropathic pain
        • Tricyclic antidepressants
          • Mech
            • Serotonin potentiates the analgesic effect of endorphins and elevates pain thresholds, serotonin re-uptake blockers are more effective than norepinephrine re-uptake blockers, e.g. trazodone (Desyrel®) blocks only serotonin.
            • Some benefit may also derive from the fact that many patients with chronic pain are depressed.
          • Eg
            • Amitriptyline (Elavil®) 75mg daily
          • Side effects limited its use
            • Anticholinergic side effects
              • Orthostatic hypotension, especially in the elderly.
              • ❌ Not recommended for use in patients with ischemic heart disease
            • Central side effects
        • Gabapentin
          • Effective in
            • Postherpetic neuralgia (PHN)
            • Painful diabetic neuropathy.
            • Trigeminal neuralgia,
            • Cancer,
            • Multiple sclerosis,
            • HIV-related sensory neuropathy,
            • CRPS,
            • Spinal cord injury,
            • Postoperative state,
            • Migraine
        • Lidocaine patch (Lidoderm®)
          • May be effective.3 ℞: apply patch for up to 12 hrs/day up to a maximum of 3 patches at a time to the intact skin over the most painful area (may trim patch to appropriate size). Supplied: 5% lidocaine.
        • Tramadol (Ultram®)
          • A centrally acting analgesic

Spinal cord processing

  • Experience of pain is described as distributed in three dimensions:
    • Cognitive
      • Frontal and limbic areas are believed to subserve the cognitive-evaluative component of pain.
    • Affective
      • Limbic cortex, cingulum, hypothalamus, thalamus, and various midbrain regions are thought to contribute to the motivational-affective component of pain.
    • Sensory
      • Primary somatosensory cortex, thalamus, spinothalamic tract, and local nerve endings are involved in the sensory component of pain.
  • Gate theory of pain
      • The gate control theory of pain states that when a stimulus gets sent to the brain it must first travel to three locations within the spinal cord:
        • Substantia gelatinosa
          • Located in the dorsal horn
          • Second-order neurons in the nociceptive pathways are present primarily in the superficial layers and in laminae V and VI of the dorsal horn and are usually divided into two classes:
            • WDR neurons
              • Receive convergent inputs from both nociceptive and nonnociceptive primary afferents.
              • Exhibit low thresholds, within the innocuous range, but unlike low-threshold tactile dorsal horn neurons, WDR neurons code stimulus intensity through the noxious range
              • WDR neurons are distributed somatotopically within the dorsal horn, and although receptive fields are relatively large, they are not so large as to preclude a contribution to stimulus localization. WDR neurons are more common in the deeper dorsal horn but are also present more superficially, in laminae I and II.
            • Nociceptive-specific neurons
              • Do not receive nonnociceptive input and respond exclusively to noxious stimuli, carried either by A delta mechanoreceptors or by both A delta and C nociceptors. Their receptive fields are small, which indicates an important role in stimulus localization. They are concentrated in the more superficial layers.
        • Fibers in the dorsal column
          • The classic view that ascending pathways through the dorsal columns are involved exclusively in transmission of nonnoxious information has been called into question by evidence that a postsynaptic dorsal column component contributes to visceral pain sensibility.
          • These studies were motivated by the clinical observation that midline myelotomy relieved pain in patients with cancer involving pelvic visceral structures.
          • Experimental studies subsequently revealed a significant projection ascending ipsilaterally through the dorsal columns and transmitting information to the ventroposterolateral nucleus of the thalamus.
            • Of importance is that this pathway may not contribute to pain sensation under normal conditions, but it could become sensitized by visceral inflammation.
        • Transmission cells in the dorsal horn
      • Sensation of pain that an individual feels is the result of the complex interaction among these three components of the spinal cord.
      • Using gate theory to help with pain
        • Hence rubbing of the injured area promotes proprioceptive (i.e. large diameter) fiber input and reduces pain perception.
        • Transcutaneous Electrical Nerve Stimulation (TENS)
          • Activate A-β fibers → activates the pain gate mechanism to inhibit pain signals going up to the brain → reduces the sensation of pain
      notion image
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      • As long as inflammation is present it will cause primary hyperalgesia
      • This is how NSAIDs help with pain
      notion image
  • Transmission of pain to brain:
      • Ascend through the anterolateral quadrant
        • Importance of the anterolateral systems in pain (and temperature) sensibility is confirmed by the ability of anterolateral cordotomy to relieve pain, at least in the short term,
        • Spinomesencephalic pathway
          • ? Paleospinothalamic pathway
          • They don't decussate at the level they enter but instead goes cranially and decussate at the midbrain
          • Activate descending pathway
            • Red NA: rostral ventromedial medulla
              • Antidepressant
            • Green 5HT: Locus cerulence
          • Role in conscious sensation, but these pathways may be more important for arousal, for autonomic and motor responses to noxious inputs, and for recruitment of descending control systems (see “Descending Modulatory Systems” section).
        • Spinoparabrachial
          • Comprises projections of neurons primarily in lamina I and relays information to the amygdala and hypothalamus, as well as midbrain PAG and caudal ventrolateral medulla.
          • Function
            • Emotional and autonomic aspects of pain
        • Spinothalamic
          • Spinothalamic tract also carries nonnociceptive information (innocuous warming and cooling, innocuous tactile information).
        • Spinoreticular pathway
          • Role in conscious sensation, but these pathways may be more important for arousal, for autonomic and motor responses to noxious inputs, and for recruitment of descending control systems (see “Descending Modulatory Systems” section).
        • Ventrolateral Funiculus (VLF) pathway
          • Loy 2002
          • Involved in locomotion.
            • Which are responsible for fictive locomotion in decerebrate preparations,
          • Pathways derived from the
            • Mesencephalic locomotor region
            • Pontomedullary medial reticular formation
          • Project to the thoracolumbar levels of the spinal cord via reticulospinal axons in the VLF
        • Dorsal Longitudinal Fasciculus (DLF)
          • Is a white matter fiber tract located within the periaqueductal gray matter of the dorsal tegmentum of the brainstem
          • It contains both ascending and descending tracts,
          • Link the forebrain and the visceral autonomic centers of the lower brainstem
            • The DLF conveys both visceral motor signals and sensory signals
              • The ascending tract of the DLF originates in the nuclei of the reticular formation and its fibers synapse in the hypothalamus, conveying visceral information to the brain
              • The descending portion of the DLF originates in the hypothalamus, descends through the brain stem periaqueductal gray matter along the base of the fourth ventricle, and continues into the spinal cord where they synapse with preganglionic autonomic neurons1.
          • Role in the pain-relieving effect of spinal cord stimulation
            • Activation of the dorsal columns is relayed to supraspinal centers, involved in pain modulation, probably via the descending fibers in the DLF.
            • The DLF is thought to play a significant role in the attenuation of pain-related signs by spinal cord stimulation
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Central processing

Sensitization through NMDA receptor through C fibres The neurons can develop changes to the pain → can be permanent forming chronic pain Phantom limb pain: Spinal anaesthetic used during procedure to reduce central sensitization
Sensitization through NMDA receptor through C fibres
The neurons can develop changes to the pain → can be permanent forming chronic pain
Phantom limb pain: Spinal anaesthetic used during procedure to reduce central sensitization
Relief pain by targeting cingulate gyrus
Relief pain by targeting cingulate gyrus
 
  • Cortical control centers for pain
    • Psychological factors contributed to pain as well.
    • Are responsible for the effects of cognitive and emotional factors on the pain experienced.
    • A negative state of mind serves to amplify the intensity of the signals sent to the brain as well
      • Eg:
        • Somebody who is depressed has a “gate” that is open more often, allowing more signals to get through, increasing the probability that an individual will experience pain from an otherwise normal stimulus.
        • Unhealthy lifestyle choices will also result in an “open gate,” which in turn leads to pain that is disproportionate to the stimulus.
  • Supraspinal Nociceptive Targets
      • Periaqueductal gray stimulation
      • Activates enkephalin-releasing neurons that project to the nucleus raphe magnus, 5-HT release activates projections to inhibitory interneurons in Laminae II (substantia gelatinosa).
      • This results in release of either enkephalin or dynorphin (endogenous opioid neurotransmitters), which bind to mu opioid receptors on the axons of incoming nociceptive C and A-delta fibers, inhibiting the release of substance P/glutamate from then and activation of ascending pain pathways.
      Thalamus
      • Pain is conducted via 2 systems:
          • Medial system
          • Medial and intralaminar thalamus pathway encodes affective aspects of pain.
            • Eg unpleasantness and emotions.
          • Function as a relay, defending against 'nociceptive aggression'.
            • They maintain a gate control function, propagating salient noxious stimuli and suppressing others.
            • This function may be disturbed in specific pain syndromes, like deafferentation pain.
          • Comprises of
            • Medial and intralaminar nuclei, along with their targets in the ACC and medial prefrontal cortices
            • Intralaminar Nuclei
              • A “nonspecific” medial complex that sends diffuse projections to the entirety of cerebral cortex.
              • Inputs
                • Spinothalamic tract (deep dorsal horn of the spinal cord)
                • Spinotrigeminal tract (Spinal trigeminal nucleus)
              • Intralaminar nuclei postulated to be involved in nociception include the
              • Outputs
                • Diffusely to the cortex
                  • Including the posterior parietal and motor cortex
            • Ventral Caudal Part of the Medial Dorsal Nucleus
              • This area of medial thalamus is often grouped with the intralaminar nuclei because of similarities in afferents and physiology,
              • Inputs
                • Spinothalamic projection from lamina I of the spinal cord.
              • Outputs
                • Primarily to the ACC and frontal lobe
              • Function
                • Motivational aspects of pain.
          • Clinical
            • Opioid analgesics inhibit activity in the medial and intralaminar thalamus.
            • Ablation and high-frequency DBS interfere with aberrant activity in the intralaminar thalamus in pain syndromes.
          Lateral system
          • Is most strongly linked to the processing of sensory-discriminative information related to pain
          • Link with lateral somatosensory cortices.
          • Receive direct spinothalamic input from both
            • Superficial layers of the dorsal horn
            • Deep layers of the dorsal horn.
          • Comprises of
              • Ventrocaudal (Vc) nucleus.
              • Principal sensory nucleus of the thalamus
              • Spinothalamic/trigeminothalamic terminations are interdigitated with terminals of the medial lemniscal pathway, wherein somatotopically organized tactile information is carried through the dorsal columns and relayed through the dorsal column nuclei.
              • Has the same medial-lateral somatotopic organization as the lemniscal pathway.
              • Outputs
                • Primary somatosensory cortex (SI) (Main)
                • Secondary somatosensory cortex (SII)
                • Insula
                • Posterior parietal cortex
              • The Vc nucleus receives visceral, as well as cutaneous, input and neurons in this nucleus have been shown to respond to noxious visceral stimuli, although the organization of responsive neurons is not apparently viscerotopic.
              • Stimulation of Vc neurons in humans most often produces contralateral, nonpainful paresthesias even at high intensities, at least in patients without a chronic pain complaint, although temperature and pain sensations can be evoked from some sites at the lowest stimulus intensity.
              • In humans, lesions of the Vc nucleus and, more broadly, the lateral thalamus have been attempted for the treatment of neuropathic pain, with resulting decreases in contralateral detection of thermal and mechanical pain, as well as in touch and proprioception.53-55 However, such surgeries are necessarily conducted with caution because of the risk of triggering iatrogenic central pain.
              Ventral posterior inferior (VPI) nucleus (aka Ventralis Caudalis Parvocellularis)
              • Fx A nociception relay centre
              • Primate studies show inputs to VPI traveling via the spinothalamic tract, arising from neurons in laminae I, IV, and V.
              • The VPI differs from the neighboring ventral posterior complex in that the former projects primarily to the SII and insular cortex, both of which are involved in perception of pain.
              • Stimulation of the ventralis caudalis parvocellularis apparently elicits painful sensations more reliably than does stimulation of the Vc nucleus itself
              Posterior part of the ventromedial nucleus (VMpo)
              • Function
                • Main thalamic relay for sensory-discriminative information,
              • Output
                • With the insula as the principal cortical target.
                • Primary somatosensory cortex (SI)
              • Input
                • Direct spinothalamic inputs from lamina I
              • Location
                • Caudal aspect of the thalamus
                  • In a location that was formerly considered part of the posterior complex.
      • Thalamic processing of pain
      Cortex
      • There is no specific cortical location in which creating a lesion eliminates pain.
      • No single cortical “pain center” mediates all aspects of the complex sensation that is pain.
        • Rather, a reasonably well-defined cortical network is recruited (pain matrix) as a result of acute noxious stimulation.
          • Although no lesion in a single site can eliminate the perception of pain, stimulation of any one of many sites can elicit painful perceptions, in conjunction with or independent of other somatosensory sensations.
      Primary Somatosensory Cortex
      • Part of the anterior parietal lobe
      • Location
        • Postcentral gyrus
      • Function somatosensory and mechanosensory function
      • Input
        • Primary thalamic input via ventral posterior nuclei of the thalamus
          • Receives both spinothalamic and lemniscal projections.
      Secondary Somatosensory Cortex
      • Location
        • On the parietal operculum at the superior bank of the sylvian fissure
      • Function
        • Specifics of pain processing are still being described,
        • SII has an unambiguous role in cortically mediated nociception.
        • SII is proposed to be involved in recognition of painful and thermal stimuli, pain-related learning, and integration of tactile and nociceptive information.
      • Input
        • Thalamic input via VPI.
        • Individual neurons in the SII may be nociceptive specific and tend to have large receptive fields, with contralateral or bilateral activation.
      Insula
      • Considered a central structure in the "pain matrix" and is the most commonly activated site in cortical imaging studies on pain.
      • fMRI indicates a somatotopic organization.
      • Subdivisions along the anterior-posterior axis are commonly used.
        • The anterior or middle/anterior insula is often implicated in nociceptive information processing.
        • The posterior insula is more involved in tactile processing.
      • Function
        • Encoding the intensity or magnitude of sensory stimuli, including painful stimuli.
          • Stimulation of the insula can result in
            • Somatosensory responses (temperature, pain, paresthesias)
            • Non-somatosensory responses like pharyngolaryngeal constriction and interruption of speech
          • Patients with lesions localised to the insular cortex may show an increase in pain tolerance or loss of the affective quality of pain while retaining their ability to detect intensity and heat-pain thresholds.
        • Integration of sensation
          • The insula has a somatotopic pain map overlaping with a non-pain somatotopic map
      Anterior Cingulate Cortex (ACC)
      • Encompassing Brodmann areas 24 and 32
      • Not somatotopic arranged.
      • Functionally divided into two manners
          • Anterior segments
          • Posterior segments
          • Midcingulate cortex
            • The primary site of activation in the cingulate cortex in response to noxious stimuli is the rostral ACC or midcingulate area.
            • The rostral segment of the ACC is primarily activated with anticipation of pain or early onset of a painful stimulus, while the caudal ACC may be activated if the stimulus is maintained.
          • ACC proper
      • Function
        • Affective (emotional) and motivational aspects of pain.
          • Excitatory stimulation of the ACC does not evoke painful sensations, though autonomic signs like changes in blood pressure and heart rate may occur.
            • This discrepancy may be due to the ACC requiring coactivation of other pain-related areas to interpret the response as painful.
          • Different patterns of activation can occur based on higher cognitive function modulation.
        • Response selection
        • Autonomic control.
      • Afferent into ACC
        • Medial thalamic nuclei
        • Mediodorsal nuclei
        • Parafascicular nuclei.
      • Clinical
        • Patients undergoing therapeutic cingulotomy for intractable pain reported only modest improvements in pain ratings, but the pain was considered less bothersome or distressing.
          • These patients also reported significant deficits in executive functioning and intention long-term.
      Prefrontal Cortex
      • The prefrontal cortex encompasses a large part of the frontal cortex anterior to the motor cortex.
      • Although no evidence exists for direct nociceptive connections, it is involved in higher cognitive function and endogenous modulation of pain.
      • It is implicated in the majority of pain-related imaging studies and even more frequently involved during chronic pain.
      • The medial prefrontal cortex and dorsolateral prefrontal cortex
        • More commonly activated during pain.
        • Also involved in
          • Executive function
          • Attention
          • Execution of high-order tasks.
        • The dorsolateral prefrontal cortex is specifically involved in the placebo response, where pain sensations are modulated by expectation.