Pain Syndromes (Week 4--Pham and Melega)

Question 1

Complex Regional Pain Syndrome (CRPS)

Answer 1

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)

Question 2

RSD and Causalgia

Answer 2

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

Question 3

Causes of CRPS

Answer 3

Sprain/strain

Post-surgical

Spontaneous

Fracture

Contusion/crush

Question 4

Mechanism of RSD

Answer 4

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

Question 5

What can acute trauma cause?

Answer 5

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

Question 6

Drugs used for descending inhibition

Answer 6

These drugs mildly enhance NE and 5HT release from descending neurons to inhibit ascenting nociceptive information

TCAs

SSRIs

SNRIs

Opioids

Tramadol

Question 7

Drugs used for peripheral sensitization

Answer 7

These drugs block the Na+ channel to decrease the hyperactivity that occurs when you have peripheral sensitization

Carbamazepine

Phenytoin

TCAs

Topiramate

Lamotrigine

Lidocaine

Question 8

Drugs used for central sensitization

Answer 8

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

Question 9

Clinical findings of CRPS

Answer 9

Pain: hyperalgesia, allodynia

Autonomic: edema, color change, temperature, sweating

Motor: tremor, weakness, contracture

Trophic: change in hair, nails, skin

Question 10

Acute phase of CRPS

Answer 10

Tender

Edematous limb

Warm

Erythema

Reduced function

Progression: (?) increasing edema, hyperhidrosis, decreased limb temperature, nail thickening, hair coarseness increases

Question 11

Dystrophic phase of CRPS

Answer 11

Ischemic phase

Still painful

Extremely cooling

Pale

Sweaty

Brittle nails

Brawny edema

Atrophy starting

Radiographic changes

Question 12

Atrophic phase of CRPS

Answer 12

Whole limb involvement

Pain variable

Skin smooth, shiny

Cool extremity

Hair loss

Tapered digits

Contractures

Atrophy

Osteoporosis

Question 13

Radiographic changes of CRPS

Answer 13

Periarticular osteopenia

Preservation of joint space though!

Prior ortho pin?

S/P Colles’ fracture?

Question 14

Psychological changes of CRPS

Answer 14

Depression

Anxiety

Fear

Anger

Failure to cope

Question 15

Diagnostic tests for CRPS

Answer 15

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)

Question 16

Treatment–functional restoration

Answer 16

Prevention

Medications

Psychiatric

Physical therapy

Interventions

Novel treatments

Question 17

Medications

Answer 17

NSAIDs/corticosteroids

Opioids

TCAs

Antiepileptic drugs

SSRIs (usually not effective)

Serotonin + NE reuptake inhibitor (SNRI: venlafaxine, duloxetine)

Adrenergic (terazosin, clonidine)

Question 18

Psychiatry

Answer 18

Evaluate for underlying disorders (major depression, personality disorder, conversion, somatization)

Teach coping strategies

Evaluate for spinal cord stimulator/pump

Question 19

Physical therapy

Answer 19

Desensitization: contrast bath, TENS trial

ROM: exercises

Edema control: gloves, elevation, massages, limb movement

Question 20

Interventions

Answer 20

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)

Question 21

Phantom limb pain

Answer 21

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

Question 22

What must phantom limb pain be differentiated from?

Answer 22

Must be differentiated from non-painful phantom phenomena, residual-limb (stump) pain, non-painful residual-limb phenomena

Question 23

Phantom limb pain as a case of maladaptive CNS plasticity

Answer 23

Evidence for reorganization of the primary somatosensory cortex in individuals with amputation

Central changes

Peripheral changes

Question 24

What seems to be the major determinant of phantom-limb pain?

Answer 24

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

Question 25

So how do A-beta afferent fibers contribute to phantom-limb pain?

Answer 25

**A-beta afferents** create **hyperexcitability** of the **spinal cord** that is usually associated with noxious input (due to **"phenotypic switch"**)

Question 26

Body-self neuromatrix

Answer 26

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**

Question 27

Hypothesis for phantom limbs using the neuromatrix

Answer 27

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**!!

Question 28

Main factors relevant for development of phantom limb pain

Answer 28

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

Question 29

Treatment for phantom limb pain

Answer 29

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

Question 30

Mirror box therapy

Answer 30

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**

Question 31

Summary of CRPS

Answer 31

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**

Question 32

When you have acute trauma, what are the molecular mechanisms of peripheral sensitization?

Answer 32

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