Management of chronic neuropathic pain after spinal cord injury

1. Management of chronic neuropathic pain after spinal cord injury Angela Mailis Gagnon MD, MSc, FRCP(PhysMed) Director, Comprehensive Pain Program Toronto Western Hospital/UHN

2. Disclosures • I have served on the Advisory Board of Lyrica (Pfizer) and Cymbalta (Lilly) (non active); • I have received unrestricted educational grants over the past 20 years from Pfizer, Purdue, Ortho Janssen, Sanofi, Valeant.

3. BACKGROUND • Spinal cord lesions are usually traumatic. • Spinal cord damage can also be the result of iatrogenic, inflammatory, neoplastic, vascular or skeletal pathology, or congenital causes. • Persisting pain is one of the commonest and most debilitating consequences of spinal cord injury (SCI).

4. Following inability to walk and bowel or bladder dysfunction, SCI patients consider chronic pain as a very disabling complication. • Psychological factors have stronger association with pain than the medical condition per se in patients with SCI pain. • Pain intensity is strongly correlated with sleep disorders, while pain, fatigue and weakness are major contributors to social disability.

5. EPIDEMIOLOGY • Estimates of the prevalence, severity and duration of pain after SCI are highly variable due to differences among the studies in regards to pain definitions, terminology, classification, inclusion criteria, reporting methods, as well as etiological and demographic factors.

6. A 2001 report reviewing132 studies, found serious methodological limitation in most. • Nevertheless, it concluded that prevalence of chronic pain after SCI varied from 40-75%. • Pain was moderate to severe in 25-60% of those with pain, often associated with psychological/ psychiatric co-morbidity and severe enough to impair daily function.

7. A 2009 lit review of 42 studies reported SCI pain prevalence 26-96%, unaffected by sex, level or type of injury. • A 2009 study reported prevalence of severe pain up to 58%, unrelated to level or type of injury. • A survey of 384 SCI community patients reported current pain in 79% of the responders, much more common in persons with less education or unemployed.

8. In summary • Chronic pain affects anywhere between 1/3 to 4/5 of patients with SCI or more • Reported as serious in many or most patients • Unrelated to gender, level or type of injury • More common in patients with lesser education or unemployed

9. PAIN LOCATIONS • In a 2001 study most common locations of current pain were: upper extremities (69%), back (61%), hips/buttocks (61%), and legs/feet (58%) • Patients with tetraplegia are much more likely to have neck/shoulder pain than those with paraplegia • Respondents reported high pain intensity, moderate activity pain interference and rated pain treatments only somewhat helpful

10. CLASSIFICATION OF SCI PAINS • The 2002 IASP Task Force on pain after SCI details mechanism of pain, system, or structure as: • a) nociceptive musculoskeletal; visceral; and neuropathic, and • b) above-level, at-level and below-level.

11. NOCICEPTIVE MUSCULOSKELETAL PAIN • Common in both acute and chronic stage of SCI • Upper extremity pain is primarily due to overuse • Spinal pain is due to fractures, surgical fixations, osteoporosis or muscle spasm • Spinal pain is more common after thoracic spinal injury, and surgical procedures within 2 weeks after the lesion

12. NOCICEPTIVE VISCERAL PAIN • Due to bladder, bowel and kidney problems • Manifested by cramps and dull pain • Associated with nausea, dysautonomia and autonomic reflex abnormalities • Autonomic dysreflexia mostly occurs with injuries above T6, manifested by episodic headaches, sudden blood pressure increase and may lead to cerebral hemorrhage

13. NEUROPATHIC PAIN PREVALENCE • Siddall showed in a 5 year follow up study of patients with SCI, prevalence of: • 41% at-level neuropathic pain • 34% below-level neuropathic pain • 5% visceral pain

14. BELOW LEVEL (CENTRAL) NEUROPATHIC PAIN • Caused by lesions of the primary somatosensory pathway, especially the spinothalamictract, and more often associated with anterior cord lesions • The causative lesion may be massive or minimal • Sensory loss varies from minimal to complete anesthesia • Pain onset is immediate or delayed (ongoing, paroxysmal or stimulus evoked)

15. NEUROPATHIC PAIN (continued) • Above-level neuropathic pain is frequently related to compressive neuropathies (e.g. CTS) • At-level neuropathic pain is related to local nerve root or spinal cord compression or damage, usually severe, seen within the first 3 months after injury and associated with allodynia • Above or at-level pain is more frequently seen after cervical spinal injuries or central cord syndromes

16. ONSET OF SCI PAIN AFTER INJURY • Immediately in 17% of the patients • less than a month in 13% • 1-6 months in 19% • 6-12 months in 8% • 1-5 years in 13%, and • after more than 5 years in 2%.

17. WORD OF CAUTION • Unusually long latencies between the injury and the development of pain should raise suspicion of cavitation (development of syrinx). • In one series, 12.6% with spinal cord lesions developed a syrinx with delayed onset of pain a year or more after SCI.

18. MECHANISMS OF SCI PAIN • In pain after SCI or brain injury, the lesion could be anywhere in the neuraxis, and is mostly associated with interruption of the spinothalamocortical nociceptive pathways. • Glutamatergic hypertonus (increased NMDA activity) is suggested by pain relief after ketamine, propofol, and barbiturates. Dorsal horn excitatory neurotransmitters play a role in at-level pain, which can progress to below-level pain.

19. PHARMACOLOGICAL MANAGEMENT • A systematic literature review (2011) shows that SCI pain poorly responds to pharmacological approaches, except for pregabalin (Lyrica). • Nevertheless, traditional pharmacological approaches include pregabalin or other neuropathic adjuvant drugs and usually strong opioids. • Medications for sleep and mood disorder may also be useful.

20. PHYSICAL & OCCUPATIONAL THERAPY • Physical therapy goal: maintain and increase strength, ROM, balance and co-ordination. • Occupational therapy goal: increase functionality through simple and complex real-life activities. • De-sensitization aims to desensitize the skin, as in the areas of transitional zone pain and hyperpathia. • A multicentre randomized controlled trial of acupuncture is currently in process in Canada

21. PSYCHOLOGICAL TREATMENTS • Main goals of treatment relate to improvement of thequality of life and earlysocial reintegration • Requires sometraining in pain-coping skills and cognitive behavioral therapy, as well as adaptation to communication, social, and sexual skills

22. SURGICAL CONSIDERATIONS FOR SCI PAIN Surgical indications: for below-level (central) SCI pains: • ongoing (steady) burning, dysesthetic pain and • intermittent paroxysmal shooting pains (neuralgic pains)

23. NEUROABLATIVE PROCEDURES • Rhizotomy, preferably percutaneous, may relieve allodynia in a single root. • Cordotomymay work better in radicular or paroxysmal pain but the effect may decrease with time. • Cordectomy includes removal of SC segment or cord transection above the level of the SCI. Works better for lesions below T10 for both ongoing and paroxysmal pains. • Dorsal Root Entry Zone (DREZ) lesion is a rather popular procedure for at-level pain.

24. NEUROAUGMENTATIVE PROCEDURES Below- level central ongoing dysesthetic pains seem to dorsal column stimulation (DCS) applicable only in incomplete SCI, and deep brain stimulation (DBS). Peripheral nerve stimulation does not have a place in the management of SCI pain. DCS, in general, is considered to have a low success rate in SCI. DBS is worth considering when DCS is technically impossible.

25. CLINICAL PEARLS AND PITFALLS • SCI pain arises from multiple mechanisms (above, at and below the level of lesion). It is a significant problem affecting 25->75% of SCI patients • Treatment must be multimodal (medications, physical modalities, psychological and interventional treatments) • The underlying pathophysiology of pains (central or peripheral, neuropathic or nociceptive) affects application of treatment modalities

26. CLINICAL PEARLS AND PITFALLS • Do not underminepsychological factors, cognition, and coping mechanisms in SCI pain and disability. • SCI patients requirepolypharmacywith opioids and neuropathic adjuvants (though only pregabalin has demonstrated a positive effect in studies). • Medications should be introducedsequentially, not simultaneously, and each trial must betime and dose contingent. • Treatment effectiveness must document pain and function.

27. ILLUSTRATIVE CASE REPORTS Case 1: Complete anesthesia/ paralysis below T6, pain right flank (BELOW LEVEL). Case 2: Partial motor/ sensory loss after T9-10 fracture, pain in both legs (BELOW LEVEL). Case 3: Incomplete SCI after C6-7 fracture/ dislocation, pain in both forearms (BELOW LEVEL). Case 4: T4 fracture with severe pain, hyperalgesia and allodynia at transitional zone (AT LEVEL) and complete motor/ sensory loss below.

28. Thank you for your attention