Traumatic or Atraumatic injury
Epidemiology
- Chronic pain following spinal cord injury effects about 70% of patients (mood, function, QOL)
- Severe pain in 30%
- Pain often nociceptive, neuropathic, or visceral
- Sociaoeconomic hardship is linked to secondary conditions and comorbidities contributing to worse QOL
- >10,000 people with SCI in Australia (300/yr) (Dr Wrigley)
- Mean age is 33yo
- Persistent pain ~80% and >50% have severe pain
- Nociceptive pain is the most common - due to trauma, muscle and joint overuse, and injury-related weakness/spasm/contractures
- Overuse, disuse atrophy, or compressive neuropathy
- Most common locations are the shoulder and the wrist
- Shoulder pain occurs in 30-70% of chronic SCI (overuse in paraplegics) "Wheelchair User's Shoulder" (Rotator cuff disease)
- Carpal tunnel syndrome in 40-60% (due to increased pressure with wrist in extreme extension)
- Fractures - Up to 70% of all SCI persons - SCI-induced bone loss (DEXA less clear)
- Most fractures around the knee (management often padded splint)
- Neuropathic pain can present acutely, or after 1 yr post injury (more likely neuropathic)
- Neuropathic pain can present at (defined as within 1 dermatome rostral and 3 dermatomes caudal), or below, the level of injury (below 3 levels caudal to the level of injury) or OTHER (no detectable noxious stimulus or inflammation or damage responsible for the pain)
- Occurs in 50% of patients
- Neuropathic pain is more common in older patients and tetraplegics
- BELOW level pain is more common in younger patients however
- Visceral pain is thought to originate from the abdomen and thorax (likely related to constipation)
Classification of the spinal injury
- ASIA classifies spinal cord injury level by the lowest spinal segment with intact sensation and antigravity muscle strength - with normal sensorimotor function above
- Either complete injury (A) (Then from A down is incomplete), Sensory incomplete (B), Motor incomplete with more than half below involved (C), motor incomplete with less than half (D), and normal (E)
Pain at-level is the level of trauma and within 3 levels above
What is the 'neurological' level of injury? The level upwards from the injury where there is normal sensation and motor power.
Often for at level pain can decrease with time whereas visceral and 'below level' neuropathic pain can worsen.
Visceral pain can worsen often due to instrumentation and complications of nerve damage to visceral organs
If a person with spinal injury has significant pain at 6 months, then this is a predictor of ongoing pain at 5 years + (Wrigley)
At level pain occurs more rapidly than below level
Maladaptive changes within the somatosensory system occur over time
Increased central sensitisation
Hyperexcitability in the spinal cord occurring over time
Classification of pain:
The International Spinal Cord Injury Pain (ISCIP) classification 2012
Musculoskeletal
Occurs in areas where some sensation remains
Described as dull or aching
Made worse by movement or posture changes
Often tenderness of associated structures on examination
Can be secondarily complicated by pathoanatomical damage
Visceral pain
Typically in the abdomen, thorax or pelvis
Dull or cramping in nature
Symptoms can often be unpleasant, unusual, and hard to localise/interpret
At-level neuropathic pain
Electric shock like, sharp, shooting, squeezing, burning
Unilateral or bilateral
Usually in a segmental pattern within a dermatome of the neurological level and/or within three dermatomes below this
Can occur from damage to the spinal nerve roots or the cord itself
Post-traumatic syrinx formation can be a cause
Below-level pain
Similar descriptors as for at-level pain
Below 3 dermatomes below the neurologic level of injury
Pain can be triggered by sudden noises, vibration, jarring etc
Can be exacerbated by visceral triggers such as UTI, constipation or skin issues
Often starts months or even years after the injury.
Usually the most excruciating.
Pathophysiology
Neuropathic
- Structural neuroplasticity and sprouting of new dendritic fibres is critical for recovery and it is these changes that may add to neuropathic pain, muscle spasticity, and autonomic dysreflexia
AT level of injury - Neuropathic pain is thought to be from hyper-excitable neurones with exagerrated responses to stimuli at or below the normal activation threshold
Multiple factors contribute, similar to sensitisation, including NMDA and glutamate receptors, Na and Ca channel changes, increased glial activation, and hypofunction of inhibitory processes/neurones.
BELOW level of injury is a bit more unclear. Because complete severence means the problem is coming from above that level. So perhaps disinhibited polysynaptic pathways, sensitised spinothalamic tract, or something more brain related (thalamic, or cortex)
Presentation
- Range of symptoms to look for - allodynia, hyperaesthesia, dysaesthesia, and paraesthesia
(patients often have trouble describing it)
Examination
-
Weakness can occur in a lower motor neuron- or upper motor neuron-type injuries. The location of the weakness of the upper motor neuron lesion does not always correspond to the expected pattern. The supply of the upper motor neurons begins in the prefrontal motor cortex, passes through the internal capsule and brainstem, and projects into the spinal cord. The supply of the lower motor neuron begins in the anterior horn cells of the spinal cord and includes the spinal roots, plexus, and peripheral nerves. Most lesions in the cervical and thoracic cord cause predominantly upper motor neuron injury.
Upper motor neuron lesions are associated with upper motor neuron lesions findings such as hyperreactive muscle stretch reflexes, clonus, Babinski sign, and detrusor overactivity and/or detrusor-sphincter dyssynergia.
indings of lower motor neuron lesion are characterized by hyporeflexia, flaccid weakness, and significant muscle atrophy. The terminal segment of the spinal cord, the conus medullaris, is located approximately at the L1 to L2 vertebral body. The lesions at the upper lumbar vertebral bodies can present with a mixture of upper and lower motor neuron lesion findings. The injuries below the L2 vertebral body may cause lower motor neuron-type injury
Reduced tendon reflexes indicate a sensory problem or segmental reduction in motor performance. Enhanced reflex activities indicate reduced descending inhibition and are therefore associated with upper motor neuron problems.
It is widely assumed that LT assesses the integrity of the dorsal (posterior) column pathway and PP the spinothalamic (anterolateral) pathway in the spinal cord.
Investigations
Treatment
Unfortunately, due to the small number of patients with SCI compared to other conditions and few large centers, large randomized clinical trials, long-term studies, and head-to-head comparisons evaluating treatment options for SCI-related pain are lacking (10).
Medication recommendations are largely based on small studies in addition to extrapolation from trials for neuropathic pain management. (10)
SCI-related pain is difficult to manage with available treatments only being able to reduce pain by about 50% in many cases
Good tip: Is the pain in a region of NORMAL sensation? If not then probably neuropathic
Non-pharmacological
- Multidisciplinary approach
- Treatment steps similar to all other types of chronic pain
- Desensitisation, orthotics (e.g. compression gloves), CBT, TENS/Massage
- Mindfulness therapies can be helpful for depression and anxiety but has minimal impact upon pain experience (7)
Pharmacological
- Muscular spasm should be treated with spasmolytics such as baclofen
- TCA --> Anti-convulsants/pregabalin (Pregab has better evidence here than Gaba) --> Tramadol --> Duloxetine (which helped less with pain specifically but reduced allodynia sensations). Need to be trialled for min 6 weeks
- Pregabalin and Gabapentin have been found to be equally efficacious (5) though other trials suggest pregabalin is more efficacious (10). The major side effects include drowsiness and somnolence. Gabapentin had less discontinuations than pregabalin. NNT = 7
- Lignocaine infusion can be trialed
- Visceral pain requires gastroenterological and urological reviews (UTIs/Constipation)
- Intrathecal baclofen has shown improvements in not only spasm but the allodynic pain sensations and is an area of further research
Surgical / Interventional
- Compression neuropathies, syringomyelia drainage, and DREZ lesioning
- Chronic wheelchair use can cause carpal tunnel, ulnar nerve entrapment, thoracic outlet syndrome, and pudendal neuropathy
- Pudendal neuropathy - Its treatment includes alterations to wheelchair ergonomics, physical therapy, analgesia, steroid injections around the ligaments and nerve canal, pulsed radiofrequency ablation of pudendal nerve, and surgical decompression as a last resort.
- Syringomyelia can present with pain at the level of injury and new neurological deficit - diagnosed by MRI. It is blockage of CSF due to vertebral disc compression, arachnoiditis, or both - treatment requires shunting, arachnoid grafting, and duraplasty
- Neurostimulation can be considered as a last resort (though has low/no evidence) (6)
(10) - Treatment
A randomized controlled study has demonstrated effectiveness of lamotrigine in patients with incomplete SCI-related evoked and spontaneous pain. Another study, mentioned above found effectiveness of lamotrigine as well as amitriptyline in improving pain relief compared to baseline pain intensity. Among the anticonvulsants, lamotrigine may be considered a second-line agent for treatment of SCI-related CP.
Levetiracetam at 1500 mg twice daily and valproate have been shown to be ineffective in SCI-related CP. Although topiramate and carbamazepine have been shown to be effective in case reports, there is currently insufficient evidence to recommend anticonvulsants besides lamotrigine for treatment of SCI CP.
Opioids, Intravenous, and Intrathecal Medications
There is limited evidence for the role of opioids, intravenous , and intrathecal medications in SCI CP. Further evidence is needed before the following medications can be recommended for use in SCI-related CP. Intravenous medications are limited by their duration of action and may have a limited therapeutic role in the long-term management of pain in this condition. Some medications, such as intrathecal baclofen, may have potential to worsen SCI-related CP.
Lidocaine
Intravenous lidocaine has been reported to be helpful in reducing SCI-related central pain and allodynia and hyperalgesia. Two studies evaluating intravenous lidocaine at a dose of 5 mg/kg infused over 30 minutes demonstrated significant pain relief over placebo. In another study, intravenous ketamine at 0.4 mg/kg and lidocaine 2.5 mg/kg given over 40 minutes found that ketamine, but not lidocaine, had a significant analgesic effect. Topical 10% lidocaine has also been reported to reduce at- or below-level SCI-related pain.
Ketamine
In small studies, ketamine has been shown to have some effect in SCI-related CP as mentioned above. In one study of 40 patients, intravenous ketamine improved pain intensity up to 2 weeks after injection. Another positive study used an oral 5 mg test dose of ketamine to select patients for intravenous infusions. Intravenous ketamine combined with alfentanil has demonstrated a significant reduction of continuous pain, allodynia, and wind-up phenomenon.
Opioids
Intravenous morphine was ineffective in the only double-blind placebo-controlled study which included patients with SCI-related pain. In another study, intrathecal morphine or clonidine was not effective in improving pain; however combination intrathecal morphine and clonidine impacted pain symptoms. Drug level in the cervical cerebrospinal fluid correlated with pain relief.
There is some evidence that tramadol may improve SCI-related neuropathic pain, but as with other opioids, substantial adverse effects may limit its use. One small observational study demonstrated pain relief with oxycodone in combination with anticonvulsants. Opioid medications have limited evidence of long-term efficacy, and there may be concerns regarding dependence, adverse effects, and potential for abuse.
Cannabinoids
Whereas cannabinoids have been extensively studied for MS-related CP, there is only one study evaluating cannabinoids in SCI-related pain. Compared to placebo, there was no significant difference in patients with below-level SCI pain taking dronabinol or placebo.
Neuromodulatory Pain Techniques
Neurosurgical and functional modulation therapies have become important alternative strategies to pharmacological therapy of SCI-related CP. Current studies are limited by sample size or quality, with many retrospective studies lacking pain characteristics or level of SCI. Invasive procedures such as deep brain stimulation are not recommended given that they are invasive, irreversible procedures with limited efficacy. Noninvasive neuromodulation may be effective in a subset of the population and needs further research.
Spinal Cord Stimulation
Spinal cord stimulation has been studied extensively for failed back surgery syndrome and complex regional pain syndrome, but studies in spinal cord injury patients with central pain are limited. Spinal cord stimulation is based on Melzack and Wall’s gate theory and works by stimulating large dorsal column fibers via electrodes placed in the epidural space. Case series have reported a relatively poor outcome in SCI patients compared to patients who experience pain relief for failed back surgery. Newer technologies with high frequency and burst paradigms have been reported to be effective for below-level SCI pain, even in cases of complete paraplegia. SCS has been reported to be more effective for incomplete lesions and for at-level pain; however efficacy of SCS often decreases over time. Currently, there remains insufficient evidence to recommend spinal cord stimulation for treatment of SCI-related central pain.
Deep Brain Stimulation
Deep brain stimulation involves implantation of a neurostimulator which targets a specific region of the brain which may potentially cause depolarization of surrounding neurons and mimic lesioning of that brain region. In a systematic review of patients evaluating DBS, patients with SCI-related central pain had poor long-term responses, with 3 of 19 patients (16%) responding to deep brain stimulation. Given the risk of infection, seizures, and intracranial hemorrhage associated with DBS, it is not recommended for treatment of SCI-related CP.
Motor Cortex Stimulation
Motor cortex stimulation has been used to treat SCI-related CP with mixed results. Noninvasive methods of brain stimulation include repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), whereas invasive methods include epidural motor cortex stimulation (EMCS). Repetitive transcranial magnetic stimulation delivers impulses in trains with a constant frequency and intensity, whereas tDCS delivers direct low-intensity electrical currents. Mechanisms of action of these devices are not well understood; however, it has been hypothesized that repetitive currents affect synaptic efficacy and result in long-term potentiation, whereas hyper- or depolarization of neuronal membranes can occur via application of a direct current. Small series of transcranial magnetic stimulation have had mixed results, and a systematic review failed to show a significant difference between TMS and sham. There is evidence that tDCS may reduce pain in the short to medium term and may be a predictor of the effectiveness of ECMS. Motor cortex stimulation remains a promising technique for long-term pain control in SCI-related injury, and further studies are needed.
Other Treatment Modalities
Alternative pain management techniques should be included in treatment of patients with central pain. Referral for educational, cognitive, and behavioral therapies has shown to have various benefits for patients with SCI-related pain. Applied relaxation and meditation techniques reduce muscle tension and improve pain coping. Cognitive behavior therapy results in decreased pain-related disability, reduced anxiety, and increased participation in activities of daily living. Referral for psychotherapy can help minimize anxiety-related to pain, reduce depression, and improve quality of sleep.
Prognosis:
Sadly only 1/3rd of patients will achieve 50% reduction in pain
Golden pearls
Past exam questions:
2016 - VIVA 1
A 43 year old woman presents to you as an outpatient for pain management. 12 months ago she presented for a micro-discectomy at C5/6 because of a herniated intervertebral disc causing a left C6 radiculopathy. Following this operation the patient awoke quadriplegic and has remained so. She complains of ongoing chronic pain and spasticity in the neck, trunk and all 4 limbs.
What is the prevalence of chronic pain following spinal cord injury?
Quiz
References / Articles / Resources
G Hadjipavlou, BMBCh MA FRCA, A M Cortese, MD, B Ramaswamy, MD FCARCSI MFPMRCA, Spinal cord injury and chronic pain, BJA Education, Volume 16, Issue 8, August 2016, Pages 264–268, (https://academic.oup.com/bjaed/article/16/8/264/2364840)
Widerström-Noga, E. Neuropathic Pain and Spinal Cord Injury: Phenotypes and Pharmacological Management. Drugs77, 967–984 (2017). https://link.springer.com/article/10.1007%2Fs40265-017-0747-8#citeas
Burke, D., Fullen, B. M., Stokes, D., & Lennon, O. (2017). Neuropathic pain prevalence following spinal cord injury: A systematic review and meta‐analysis. European Journal of Pain, 21(1), 29-44. https://onlinelibrary.wiley.com/doi/full/10.1002/ejp.905
Powerpoint lecture - https://www.academyscipro.org/wp-content/uploads/2017/09/Trevor-A.-Dyson-Hudson-M.D.-SCI-Review-Course_Pain-MSK-in-SCI-2017-FINAL.pdf
Davari, M., Amani, B., Amani, B., Khanijahani, A., Akbarzadeh, A., & Shabestan, R. (2020). Pregabalin and gabapentin in neuropathic pain management after spinal cord injury: a systematic review and meta-analysis. The Korean journal of pain, 33(1), 3–12. https://doi.org/10.3344/kjp.2020.33.1.3 Pregabalin and gabapentin in neuropathic pain management after spinal cord injury: a systematic review and meta-analysis (nih.gov)
Huang, Q., Duan, W., Sivanesan, E. et al. Spinal Cord Stimulation for Pain Treatment After Spinal Cord Injury. Neurosci. Bull.35, 527–539 (2019). https://doi-org.ezproxy.library.sydney.edu.au/10.1007/s12264-018-0320-9 Spinal Cord Stimulation for Pain Treatment After Spinal Cord Injury | SpringerLink
Hearn, J.H., Cross, A. Mindfulness for pain, depression, anxiety, and quality of life in people with spinal cord injury: a systematic review. BMC Neurol20, 32 (2020). https://doi.org/10.1186/s12883-020-1619-5
Ong, B., Wilson, J. R., & Henzel, M. K. (2020). Management of the patient with chronic spinal cord injury. Medical Clinics, 104(2), 263-278. Management of the Patient with Chronic Spinal Cord Injury - Medical Clinics (theclinics.com)
Kumru, Benito-Penalva, J., Kofler, M., & Vidal, J. (2018). Analgesic effect of intrathecal baclofen bolus on neuropathic pain in spinal cord injury patients. Brain Research Bulletin, 140, 205–211. https://doi.org/10.1016/j.brainresbull.2018.05.013
Noe. (2020). Pain Management for Clinicians A Guide to Assessment and Treatment (1st ed. 2020.). Springer International Publishing. https://doi.org/10.1007/978-3-030-39982-5
Sang, & Hulsebosch, C. E. (2021). Spinal Cord Injury Pain. Elsevier Science & Technology.
Comments