Pain Syndromes (Week 4--Pham and Melega) Flashcards
Complex Regional Pain Syndrome (CRPS)
Type I (Reflex Sympathetic Dystrophy–RSD) and Type II (causalgia–nerve damage)
Pain is hallmark and is regional/disproportionate
Signs of vasomotor and motor dysfunction
Diagnosis of exclusion
Usually preceded by injury to single limb
Female > male (3:1)
RSD and Causalgia
What Complex Regional Pain Syndrome (CRPS) used to be called? Now the two types??
RSD (Reflex Sympathetic Dystrophy): disproportionate pain, autonomic dysfunction, sympathetically maintained pain
Causalgia: described in WWII, persistent burning pain following gun shot wound
Causes of CRPS
Sprain/strain
Post-surgical
Spontaneous
Fracture
Contusion/crush
Mechanism of RSD
Original injury initiates pain impulse carried by sensory nerves to CNS
Pain impulse triggers impulse in sympathetic nervous system which returns to site of injury
Sympathetic impulse triggers inflammatory response causing vessels to spasm leading to swelling and increased pain (get burning extremity pain, red mottling of skin)
Pain triggers another response, establishing a cycle of pain and swelling
What can acute trauma cause?
Release of “algesic soup” that can result in sensitization of primary afferent neurons and neurogenic inflammation:
Substance P can increase vascular permeability, induce release of cytokines, attract leukocytes to site of injury (SP also causes release of bradykinin)
Bradykinin can cause vasodilation, increase SP release, sensitize nociceptors
Prostaglandins contribute to nociceptive sensitization
NE activation of peripheral nociceptive terminals (NE to alpha 1 sends out collaterals to activate C fibers)
Ectopic production of receptors (also expression of receptors of phenotype not normally expressed on nociceptor (NE, NGF))
Sprouting of new collaterals on nociceptor
Drugs used for descending inhibition
These drugs mildly enhance NE and 5HT release from descending neurons to inhibit ascenting nociceptive information
TCAs
SSRIs
SNRIs
Opioids
Tramadol
Drugs used for peripheral sensitization
These drugs block the Na+ channel to decrease the hyperactivity that occurs when you have peripheral sensitization
Carbamazepine
Phenytoin
TCAs
Topiramate
Lamotrigine
Lidocaine
Drugs used for central sensitization
These drugs block the NMDA receptor in the spinal cord to block incoming nociceptive signals to secondary neurons that occur when you have central sensitization
Ketamine
Topiramate
Dextromethorphan
Methadone
Others (don’t block NMDA receptor): capsaicin, NSAIDs, COX2 inhibitors, lidoderm patch
Gabapentin blocks Ca2+ channel
Clinical findings of CRPS
Pain: hyperalgesia, allodynia
Autonomic: edema, color change, temperature, sweating
Motor: tremor, weakness, contracture
Trophic: change in hair, nails, skin
Acute phase of CRPS
Tender
Edematous limb
Warm
Erythema
Reduced function
Progression: (?) increasing edema, hyperhidrosis, decreased limb temperature, nail thickening, hair coarseness increases
Dystrophic phase of CRPS
Ischemic phase
Still painful
Extremely cooling
Pale
Sweaty
Brittle nails
Brawny edema
Atrophy starting
Radiographic changes
Atrophic phase of CRPS
Whole limb involvement
Pain variable
Skin smooth, shiny
Cool extremity
Hair loss
Tapered digits
Contractures
Atrophy
Osteoporosis
Radiographic changes of CRPS
Periarticular osteopenia
Preservation of joint space though!
Prior ortho pin?
S/P Colles’ fracture?
Psychological changes of CRPS
Depression
Anxiety
Fear
Anger
Failure to cope
Diagnostic tests for CRPS
Plain film: osteopenia
Three phase bone scan: blood pooling; more blood in painful area (but if do this too early or too late, could be normal)
Thermography: hot zones
Sympathetic blocks: pain resolution after injection (for diagnosis need to catch it early) (put lidocaine near symp chain)
Treatment–functional restoration
Prevention
Medications
Psychiatric
Physical therapy
Interventions
Novel treatments
Medications
NSAIDs/corticosteroids
Opioids
TCAs
Antiepileptic drugs
SSRIs (usually not effective)
Serotonin + NE reuptake inhibitor (SNRI: venlafaxine, duloxetine)
Adrenergic (terazosin, clonidine)
Psychiatry
Evaluate for underlying disorders (major depression, personality disorder, conversion, somatization)
Teach coping strategies
Evaluate for spinal cord stimulator/pump
Physical therapy
Desensitization: contrast bath, TENS trial
ROM: exercises
Edema control: gloves, elevation, massages, limb movement
Interventions
Regional intravenous infusions: temporary treatment
Sympathetic blockade: stellate/lumbar sympathetic, permanent/temporary, sympathetic ganglion block, usually done in series (inject into CSF in subarachnoid space)
Surgical/chemical: permanent/temporary, 30% recurrence rates
Spinal cord stimulator: level of nerve roots, invasive, stimulator trial to be done prior to placement (over-stimulate to decrease pain eventually)
Phantom limb pain
A group of neuropathic pain syndromes characterized by pain in the amputated limb or pain that follows partial or complete deafferentation
Occurs in 50-80% of people who get amputation
Amputation followed by sensation that deafferented body part is still present
Considered neuropathic, assumed to be related to damage of central or peripheral neurons
Commonly pain is similar to pain felt in limb before amputation
Non-painful phantom sensations may include specific position, shape, movement, feelings of warmth or cold, itching, tingling, electric sensations, burning or cramping
What must phantom limb pain be differentiated from?
Must be differentiated from non-painful phantom phenomena, residual-limb (stump) pain, non-painful residual-limb phenomena
Phantom limb pain as a case of maladaptive CNS plasticity
Evidence for reorganization of the primary somatosensory cortex in individuals with amputation
Central changes
Peripheral changes
What seems to be the major determinant of phantom-limb pain?
Central changes
Increased excitability of dorsal horn neurons
Reduction of inhibitory processes
Structural changes at central nerve endings of primary sensory neurons, interneurons and projection neurons
“Phenotypic switch” in expression of neuropeptides (such as substance P) which are normally expressed by nociceptor primary afferent A-delta fibers and C fibers but now become expressed by A-beta fibers after peripheral nerve injury
Central sensitization mediated by NMDA receptor and its NT, glutamate
So how do A-beta afferent fibers contribute to phantom-limb pain?
A-beta afferents create hyperexcitability of the spinal cord that is usually associated with noxious input (due to “phenotypic switch”)
Body-self neuromatrix
The brain has a particular matrix, or map of the body, genetically determined, that both responds to stimuli from proprioception and continuously sends impulses to different parts of the body to check on the condition and location of the body parts
Factors that contribute to patterns of activity generated by this body-self neuromatrix are sensory, affective, and cognitive
Hypothesis for phantom limbs using the neuromatrix
When neuromatrix is deprived of modulating inputs from limbs, it produces an abnormal signature pattern that subserves psychological qualities of heat or burning (most common qualities of phantom limb pain)
Cramping pain might be due to messages from neuromatrix to produce movement so in absence of limbs, messages may become more frequent and stronger in attemps to move a part of the limb
Shooting pains may be neuromatrix attempting to move whole limb and thus sending out abnormal patterns felt as pain shooting down from groin to foot
Origin of these pains in the brain!!
Main factors relevant for development of phantom limb pain
Long-lasting noxious input to limb –> development of cortical pain memory and enhanced excitability –> amputation –> reorganization of amputation zone in somatosensory cortex
Selective loss of C fibers, random input from stump neuroma, abnormal changes in DRG and dorsal horn, sympathetic activation –> reorganization of amputation zone in somatosensory cortex
Treatment for phantom limb pain
Most treatments do not take account of mechanisms underlying the production of the pain
A reasonable approach to treat phantom pain is treatment for neuropathic pain
Examples: local anesthesia, sympathectomy, dorsal-root entry-zone lesions, cordotomy and rhizotomy, neurostimulation methods, or pharmacological interventions such as anticonvulsants, antidepressants and muscle relaxants
Mirror box therapy
Mirror placed so reflection of normal limb is superimposed on injured (amputated) limb
Patient moves normal limb in exercise routine and brain is “tricked” into believing that the injured (amputated) limb is functional
Use for CPRS, stroke, Phantom limb
Summary of CRPS
Can affect anyone
Clinical suspicion key in early identification and treatment of this condition
Clinical presentation varies among patients
Early treatment means better prognosis
Goal of treatment is to restore function
When you have acute trauma, what are the molecular mechanisms of peripheral sensitization?
1) Substance P released from nociceptor terminals (like normal) causes blood vessels to release bradykinin but bradykinin causes release of more SP (mini vicious cycle!)
2) Sympathetic fibers send collaterals to activate primary afferent C fibers. Now when you just want to vasoconstrict, those fibers activate primary afferent fibers by sending NE to new set of receptors on axon terminals containing SP and SP released, causing BK release, causing more stimulation of that primary afferent!
3) Primary afferent C fibers sprout collaterals that activate other adjacent afferent C fibers too
