Neuropathic Pain Flashcards
Mechanisms of neuropathic pain
Mechanical nerve injury
- Tumour compression
- Surgical resection (e.g. post mastectomy pain syndrome)
Chemical nerve injury
- Some chemotherapies may result in neuron cell death or dysfunction
Ectopic discharge following injury
- After nerve injury, nerves may display ectopic discharge and result in a barrage of nociceptive signalling without a peripheral stimulus
Alterations to sodium channels on neurons
- Nerve injury may result in greater expression of sodium channels
- May result in hyperexcitability and increased nociceptive transmission
- Pharmacologic basis of carbamazepine, lamotrigine, local anesthetics
Voltage gated calcium channels
- Play a role in permitting neurotransmitter release from the presynaptic terminal
- Modulates neuronal excitability
Nerve sheath pain
- Due to distortion of the nerve sheath and irritation to the small primary afferents that innervate nerve trunks
Secondary central pain
- Sensitization of the dorsal horn by the action of glutamate on the dorsal horn and activation of NMDA receptors
- Results in autonomous discharges in the dorsal horn can result in aberrant sensory transmission (allodynia, hyperalgesia, paradoxical heat sensation)
Qualities of neuropathic pain
Quality
- Sharp, shooting, burning, numb, stabbing
- Brief paroxysmal pain that may be spontaneous or evoked by movement
- Allodynia (painful response to a non painful stimulus)
- Hyperalgesia (Increased painful response to a painful stimulus
- Hyperpathia (delayed and prolonged response to painful stimulus)
- Dynamic mechanical allodynia
Associated features
- Neurologic deficits
- Response to opioids (likely to be reduced)
- Sensory changes
- Weakness
Onset
- May develop immediately after nerve injury/disease or as a late effect
May occur as a mixed syndrome, with nociceptive and neuropathic pain co-existing
Neuropathic pain screening tools
Leeds Assessment of Neuropathic Signs and Symptoms - validated in populations without cancer
Neurotoxic chemotherapies, clinical presentation
- Platinums
- Taxanes
- Vinca alkaloids
- Bortezomib
Affects up to 96% of patients who receive these chemotherapies, and one year after treatment still affects 50%
Typically glove and stocking distribution
- Spontaneous pain
- Paresthesias
- Allodynia
- Hyperalgesia
- Hypoesthesia (numbness)
- Impaired propioception
Features associated with neuropathic pain to consider on physical exam
- Target the affected area and look for:
- Local tumour extension (e.g. chest wall tenderness, cervical spine tenderness)
- Secondary muscle spasm in the area
- Lymphadenopathy in the area
- Range of motion of area
- Provocative manoeuevres to reproduce pain (characterise the pain syndrome, identify structures involved)
- Look for swelling/discolouration that may suggest tumour infiltration of the neurovascular bundle and venous/lymphatic obstruction - Screening neurologic exam
Spurling’s manoeuvre
Test for cervical root radiculopathy and essentially causes cervical compression.
Turn the patient’s head to the affected side while extending and applying downward pressure to the top of the patient’s head.
Positive if the pain arising in the neck radiates in the direction of the corresponding dermatome ipsilaterally.
95% sensitive and 94% specific for diagnosing nerve root pathology
Horner’s Syndrome
Miosis (constriction), facial anhidrosis, ptosis
Occurs when the ipsilateral sympathetic trunk is damaged. Classified according to extent of anhidrosis.
Anhidrosis of face, arm, and trunk:
- MS
- Brain tumours
- Lateral medullary syndrome
Anhidrosis of face:
- Cervical rib traction on stellate ganglion
- Thyroid carcinoma
- Bronchogenic CA on apex of the lung (Pancoast tumour)
- Tube thoracostomy complication
No anhidrosis
- Carotid artery dissection
- May occur during migraine attack or cluster headache
- Middle ear infection
Paradoxical heat sensation
Experience of intense heat from application of ice in the distribution of neuropathic symptoms is highly suggestive of neuropathic pain.
Lower motor neuron symptoms
- Pain
- Hypotonia
- Areflexia or hyporeflexia
- Weakness
- Numbness/parasthesias (especially saddle anesthesia in cauda equina)
- Sphincter dysfunction (later in cauda equina)
- Fasciculations
Upper motor neuron symptoms
- Pain exacerbated by recumbency, cough, sneeze, strain
- Lhermitte’s sign
- Spasticity
- Hyperreflexia below lesion
- Weakness (symmetric - typically develops to paralysis within 7 days!)
- Numbness/parasthesias (symmetric, ascending, upper level of sensory loss may correspond to location of tumour)
- Sphincter dysfunction (later)
- Spinal tenderness to percussion
Cervical radiculopathy patterns
C5:
- Muscle: Deltoid (shoulder abduction) and biceps flexion
- Sensory: Cap of shoulder/deltoid
- Reflex: None
C6:
- Muscle: Biceps (elbow flexion) and wrist extension
- Sensory: Thumb and index finger
- Reflex: Biceps
C7
- Muscle: Triceps (elbow extension), wrist flexion, finger extensors
- Sensory: Middle finger
- Reflex: Triceps
C8
- Muscle: Finger flexors and intrinsics
- Sensory: Ulnar aspect of hand
- Reflex: None
T1
- Muscle: Finger intrinsics (along with C8)
- Sensory: Medial aspect of elbow/upper arm
- Reflex: None
Features suggestive of tumour infiltration causing neuropathic pain
- High intensity
- Rapid development of neurologic signs
Investigation of neuropathic pain
- Localise the lesion as best as possible with a thorough neurologic exam
- Consider an MRI to show localization and extent of disease
EMG and nerve conduction - assess large fibre function
Nerve biopsy
Management of neuropathic pain: Pharmacologic
- Gabapentinoid (unless patient is depressed, in which case go straight to antidepressants). Note that pregabalin (Lyrica) is more rapidly and predictably absorbed.
- Analgesic antidepressants (Duloxetine is first line, then try a TCA)
- Steroids (consider more for short term pain crisis)
- Topical lidocaine 5% if localised
- If opioids are required due to moderate/severe pain, start with an IR opioid while adjuvants are being initiated and then switch to long acting once pain regime is stablised. NNT for opioids 2.6-5.1
If no response to gabapentin or antidepressants, go to other anticonvulsants (e.g. lacosamide), cannabinoid
Evidence for first line agents: each class of agents produces at least 50% pain relief in about 1/3 of patients with diabetic neuropathy or post-herpetic neuralgia
More evidence for gabapentin added to an opioid analgesic for cancer pain in RCTs, though no significant benefit found in an RCT for chemo-induced neuropathy
Second line
- NMDA antagonists (ketamine - combined with benzo or haldol for psychotomimetic side effects)
- Methadone
- Corticosteroids
- Cannabinoids
- Continuous local anesthetic infusion
Classification of Neuropathic Pain
Peripheral
- Mono/polyneuropathy (DM, EtOH, HIV, chemo)
- Plexopathy
- Radiculopathy
- Nerve injury (post surgical, post traumatic)
- Amputation (phantom limb pain, stump pain)
- Root avulsion
- Post herpetic neuralgia
- Trigeminal neuralgia
- Neoplasms
Central
- MS
- CNS neoplasms
- Spinal cord injury or compression secondary to neoplasm
- Syringomyelia
- Myelopathy
- Stroke
Definition of neuropathic pain
- Pain caused by a lesion or disease of the somatosensory system
- Prevalence of up to 40% in patients with advanced cancer
- May be a complication of anticancer therapy (surgery, rads, or chemo), malnutrition or paraneoplastic syndromes, or due to direct infiltration of pierpheral nerves by the cancer (especially in mononeuropathy or plexopathies)
Chemotherapy induced neuropathy
Typically dose-dependent, cumulative side effect with glove-and stocking distribution.
- Sensory loss
- Paresthesias
- Dysesthesias
- May be accompanied by muscle weakness
May progress after chemo is complete, but often will resolve with time
Oxaliplatin-induced neuropathy
- Acute phase of cold allodynia and pricking dysesthesia in hands and feet
- Characteristic pharyngolaryngeal dysesthesias with SOB or dysphagia induced by cold drinks
- Typically improves over time with many patients experiencing complete resolution in 6 months
Central pain
- Seen in stroke patients (8%), MS (25%), and 40-50% of patients with spinal cord
Bortezemib neuropathy
- Presents as mild-moderate sensory loss in distal extremities and painful paresthesia
- May be accompanied by autonomic symptoms (orthostatic hypotension) as well as diarrhea/constipation
Often resolves within 3 months but can persist
Herpes zoster neuropathy
- Reactivation of varicella zoster infection
- Occurs later in life, or in immunocompromised patients (e.g. HIV)
- May cause post-herpetic neuralgia- burning and paroxysmal lancinating pain in the affected dermatome
- Often associated with allodynia
Non-pharmacologic treatment of neuropathic pain
- CBT in chronic pain
- Physiotherapy to alleviate complications related to immobility or other effects of the neurologic disease
- Consider interventional analgesia
- Massage, fitness, acupuncture work for some patients.
Treatment of trigeminal neuralgia
Carbamazepine and oxcarbamazepine are first line
Treatment of focal peripheral neuropathy
Topical lidocaine patch is first line
Treatment of neuropathy in patients with depression/anxiety
- Consider SNRIs or TCAs
- Consider pre-gabalin for anxiety given evidence it can act as an anxiolytic
Treatment of neuropathy in patients with sleep disturbance
- Consider TCAs or gabapentin/pre-gabalin
