The Brain on Pain - Presentation PDF

The Brain on Pain Devin Mott PT, DPT Objectives Explain how nociception is actively perceived in the cortex Differentiate between peripheral and central sensitization Describe changes seen in chronic pain at the CNS 2 A Three Neuron Sys...

The Brain on Pain Devin Mott PT, DPT Objectives Explain how nociception is actively perceived in the cortex Differentiate between peripheral and central sensitization Describe changes seen in chronic pain at the CNS 2 A Three Neuron System Explanation of pain transmission in three parts: ○ First Afferent: transmission of nociception and temperature ○ Second Order: Spinothalamic Tract ○ Tertiary: Thalamocortical 3 Spinal Cord Location of peripheral nociceptor termination ○ Multiple primary afferent fibers may converge on one neuron at spinal cord Convergence one one neuron can be thought of as basis for referred pain Neurons of Dorsal Horn: ○ High Threshold Respond to only noxious stimulus ○ Low Threshold Respond to only innocuous stimulus ○ Wide Dynamic Range Responds to combination of noxious and innocuous 4 Central Sensitization After tissue injury; ○ High threshold and Wide Dynamic Range Neurons are sensitized Results in: Increased receptive field Increased responsiveness to sensory input Central vs Peripheral Sensitization ○ Allodynia is unique to central sensitization Secondary to increased responsiveness of wide dynamic range neurons resulting in increased responsiveness to innocuous input 5 Ascending Pathways Spinothalamic Tract ○ Projects information to: VPL Nucleus Involved in sensory-discriminative component of pain Medial Thalamic Nuclei Motivational-affective component of pain 6 Ascending Pathways Spinomesencephalic and Spinoreticular Tracts ○ Spinomesencephalic: Projects to the midbrain (specifically PAG) PAG is responsible for descending inhibition ○ Spinoreticular: Projects to the brain stem Plays a role in activation of endogenous opioid system Signals homeostatic changes in response to pain 7 At the Brain Neurotag: also called cortical representation or neural representation ○ A network of interconnected neurons ○ Activation of a neurotag will produce a specific outcome Activation of neurotags require: ○ Member neurons need to fire ○ Nearby neurons need to not fire 8 Neurotags Can be discriminated as a primary or secondary neurotag ○ Primary: effects action (produces an outcome) ○ Secondary: modulation of neuronal mass and precision Strength of a neurotag will determine the influence on the outcome ○ Larger neurotags will predominate over smaller ones ○ Precise neurotags will predominate over imprecise ○ Neuroplasticity The nervous system will undergo structural and functional changes based on activity and reinforcement https://bjsm.bmj.com/content/bjsports/50/16/990.full.pdf 9 Neurotags https://bjsm.bmj.com/content/bjsports/50/16/990.full.pdf 10 Neurotags https://bjsm.bmj.com/content/bjsports/50/16/990.full.pdf 11 Pain Neurotags Pain can continue to exist even with removal of peripheral stimulus ○ Telling us nociception is not required for pain to occur Pain Neurotag is a primary tag responsible for output of sensation ○ Influence by secondary tags Nociception Visual detection of threats Expectation of threat Perception Social situation https://bjsm.bmj.com/content/bjsports/50/16/990.full.pdf 12 Hebbian Theory Brain Maps: ○ Constantly changing and reorganizing Hebb’s Law: Nerves that fire together wire together Neuroplasticity: brain maps for sensory, motor, emotional ○ Functional changes (increased gray matter) in areas of practice Hebb’s Law: ○ “Nerves that Wire Together Fire Together” ○ “Neurons out of sync fail to link” A brain in persistent pain will become more efficient at creating pain ○ Circuits co-existing with pain circuit Stress Anxiety Fear Pain behaviors 13 Pain and Emotions Anterior Cingulate Cortex: ○ Connections to the limbic system (emotional) and cognitive (cortex) ○ Allows for overlap of pain and brain circuits involved in: risk/reward Depression Fear Anxiety https://neuro.psychiatryonline.org/doi/10.1176/jnp.23.2.jnp121 14 FMR Studies Insula activation in pain: ○ Anterior deals with integration of emotions and interception ACC activation in pain ○ Responsible for activation of behavioral response https://journals.lww.com/pain/Fulltext/2016/06000/ Brain_activations_during_pain__a_neuroimaging.14.aspx 15 Pain Processing Patients in chronic pain lose ability to activate middle-frontal gyrus ○ Portion of the brain that activates descending inhibition Disruption in thalamocortical connectivity ○ May lead to changes in sensation, motor performance, and cognition 16 Pain and Emotions Anterior Cingulate Cortex: ○ Connections to the limbic system (emotional) and cognitive (cortex) ○ Allows for overlap of pain and brain circuits involved in: risk/reward Depression Fear Anxiety Insula Deals with self-awareness, pain processing, introception, and addiction Plays a role in assessment of intensity of pain FMR Studies Insula activation in pain: ○ Anterior deals with integration of emotions and interception ACC activation in pain ○ Responsible for activation of behavioral response Pain Processing in Healthy vs Chronic Patients in chronic pain lose ability to activate middle- frontal gyrus ○ Portion of the brain that activates descending inhibition Disruption in thalamocortical connectivity ○ May lead to changes in sensation, motor performance, and cognition Depression and Pain Impacts Psychological status of the patient at presentation has a much stronger influence on outcome than does conventional clinical information Persisting symptoms in low back pain may be due more to psychosocial influences than to medical factors Psychosocial screening and emotional distress were the only predictors that were statistically significantly associated with non-recovery at 12 Burton et al. Psychosocial Predictors of Outcome in Acute and Subacute LBP Trouble. Spine. 1995 Grotle et al. months Prognostic factors in first-time seekers do to acute LBP. Eur J Pain. 2007;11:290-298 Pincus et al. ○ 3-4 times higher odds of non-recovery than other reference A Systematic Review of Psychological Factors as Predictors of Chronicity/Disability in Prospective Cohorts of LBP. Spine 2002 2 standards 3 Acute Pain and the Brain Thalamus: sensory gateway, cortical processing Primary and secondary motor and sensory cortex: organize and prepare movement, sensory discrimination Insula: salience and awareness Basal ganglia: motor planning Prefrontal cortex: problem solving, memory Apkarian et al (2005) E J Pain 2 Cingulate cortex: concentration, 4 focus, cognition Amygdala: fear conditioning Chronic Pain and the Brain Amygdala: fear conditioning, aversive behavioral reactions Prefrontal cortex: problem solving, memory, role in negative cognitions Basal ganglia: integration of Hashmi et al (2013), Mutso et al (2013), Fasick et al (2015) 2 5 motor, emotional, autonomic and cognitive responses to pain Acute vs Chronic Pain on the Brain Acute/Subacute Pain Chronic Pain Sensory/Nociceptive Limbic/Emotional/Frontal Pattern Pattern 2 6 Acute Pain (Nociception) Thalamus ○ Sensory gateway, cortical processing Primary and secondary somatosensory & motor cortices ○ Organize and prepare movement, sensory discrimination Insula ○ Salience & awareness Basal ganglia ○ Motor planning Prefrontal cortex ○ Problem solving, memory Cingulate cortex ○ Concentration, focus, cognition Amygdala Chronic Pain Prefrontal cortex ○ Problem solving, memory, role in negative cognitions Amygdala ○ Fear conditioning, aversive behavioral reactions Basal ganglia ○ Integration of motor, emotional, autonomic and cognitive responses to pain Hippocampus & nucleus accumbens ○ Increased connectivity with prefrontal cortex Chronic Pain and Brain Activation Transition to chronic pain results in a large‐scale spatial shift in processing: ○ The pain neuromatrix is distinct (non‐overlapping) between chronic and acute/subacute states ○ Not simply a reinforcement of the nociceptive system or acute/subacute pain neuromatrix ○ Reduced activation threshold in the pain neuromatrix ○ Shift is toward limbic/emotional/frontal processing ○ Different emotions, stress, other inputs can more easily activate or modulate the pain neuromatrix ○ Reduced capacity to regulate and adapt behaviorally in emotional, attention, and cognitive domains Chronic Pain and Shift in Processing Occurs during the first year (especially 3 to 12 months) ○ Shift from a nociceptive‐sensory pattern in acute pain to one of emotional and reward circuitry ○ Heightened connectivity between prefrontal cortex, hippocampus, nucleus accumbens, amygdala and basal ganglia (cortico‐mesolimbic) ○ Global gray matter atrophy equivalent to 10‐20 years of aging (nearly 1.5cm3 of gray matter loss per year of chronic pain); esp. noted in thalamus, prefrontal cortex, basal ganglia, insula, cingulate cortex Brain Structural Changes Brain Structural Changes: ○ The areas with gray matter loss are associated with cognitive, affective and perceptual functional domains (not just in typical pain matrix areas) ○ Likely relates to comorbidities of fatigue, cognitive and emotional impairments ○ Hippocampus and parahippocampal gyrus demonstrated increased volume Shift in Brain Processes What About Other Brain Changes? ○ Brain physiologic changes: Glial cell activation Alteration of blood brain barrier Development of a pro‐inflammatory profile (cytokines IL‐1b, IL‐6, TNFa); heightened immune‐ brain communication Chronic Pain and Gliopathy Staged responsiveness after injury or inflammation (or chronic opioids): satellite cells mobilize in 4 hours, microglia in 2 days, astrocytes 14 to 150 days! ○ Sensitive to and can release neurotransmitters and immune molecules (cytokines IL1, IL6, IL18, TNFa and chemokines) to modulate neuronal and synaptic activity ○ Can release anti‐inflammatory cytokines (IL4, IL10, TGF‐B) ○ Glial‐immune interactions – widespread consequences to the pain experience