9 minute read
Pain in the brain
Pain in the brain
The International Association of Pain updated their definition of neuropathic pain (NP) in 2018. According to the new definition, NP is caused by a lesion or disease of the somatosensory nervous system. The old definition described it as ‘pain initiated or caused by a primary lesion, dysfunction or transitory perturbation of the peripheral or central nervous system (CNS)’.1
Advertisement
Limited data are available on the prevalence of NP in South Africa. International studies estimate that the prevalence of NP is between 7%-8% in the general population. However, if conditions such as diabetes (26%), herpes zoster/ shingles (19%), and postsurgical pain (10%) are included in estimates, the incidence is much higher. Furthermore, 35% of patients with HIV experience NP.1,2,3,7
What causes neuropathic pain?
Patients often use words such as burning, pins and needles (paresthesia), tingling, numbness, electric shocks/shooting, crawling (formication), itching, and intolerance to temperature, to describe their experiences.3
In more advanced cases, patients may describe pain arising from stimuli that are not usually painful (eg allodynia) or pain from normally painful stimuli that is out of proportion to what would be expected (eg hyperalgesia).3
Numerous causes of NP have been identified and can be broadly categorised into peripheral and central pain. The most common cause of peripheral is traumatic nerve injury (either from an accident or surgery).3,4
Other causes of peripheral NP include for example diabetic peripheral polyneuropathy, chemotherapy-induced peripheral neuropathy, radicular pain, and postsurgical chronic neuropathic pain.1,2,3
Causes of central NP include multiple sclerosis, poststroke pain, spinal cord injury–related pain, postherpetic neuralgia, complex regional pain syndrome, and trigeminal neuralgia.3
Stepwise algorithm
Bates and colleagues describe the diagnosis and treatment of NP as challenging. To aid clinicians, they developed a multidisciplinary, stepwise algorithm.4
Step 1: History and assessment
Identifying so-called red flags, which may indicate conditions that require urgent interventions (eg spinal cord compression) is the priority in assessing any pain symptoms. Secondly, the clinician should identify patients where it may be possible to treat the pain by treating the underlying cause and also to identify particular types of pain, which may require specialised treatment.4
Taking a thorough history can aid the clinician in identifying the site of pain, radiation, precipitating factors, duration, character, pattern, intensity, aggravating and relieving factors and associated symptoms.4
Apart from the symptoms mentioned above, other symptoms that may support a diagnosis of neuropathic pain include descriptions of areas of numbness or symptoms of concurrent motor or autonomic nerve involvement.4
Step 2: Quantify the consequences of pain
Poorly controlled pain impacts the quality of life (QoL) of both the patient and his/her caregiver. NP may influence the patient’s ability to take part in for example social activities and exercise. It also has an effect on his/her independence, mood and sleep. Combined, these negative consequences may impact the efficacy of pain control. Quantifying the impact on the patient’s QoL can therefore aid in decision-making regarding the management and treatment of NP.3,4
Tools that can be used in quantifying NP’s impact on the patient’s QoL include validated questionnaires. The objective of these tools is to identify the presence of NP and measure or quantifying the impact it has on the patient’s quality of life. Bates et al recommend PainDetect, Douleur Neuropathique en 4 Questions (DN4), and the Leeds Assessment of Neuropathic Symptoms (LANSS).4
The PainDetect questionnaire is completed by the patient and has a sensitivity and specificity of 85% and 80%, respectively. The DN4 questionnaire includes seven pain discriminators and three examination findings. A score of 4+ indicates that NP is likely. The DN4 has a sensitivity and specificity of 83% and 90%. The LANSS questionnaire includes five symptom descriptors and two examination findings. Its sensitivity and specificity are 82%–91% and 80%–94%. Pain intensity can be measured using the numeric rating scale and/ or the visual analogue scale.4
It is also important to keep in mind that the patient’s beliefs, attitudes, and behaviours will also influence the efficacy of pain control and ultimately outcomes. During consultations ask the patient about his/her understanding of his/ her pain, the meaning of his/her pain, his/her expectations, and goals as well as previous pain control treatment that might not have been successful.4
Step 3: Examination
According to Bates et al, about 50% of patients who experience musculoskeletal pain use words that are commonly used to describe NP (eg shooting and tingling), and 30% of patients with non-NP will describe burning. As a result, it is often difficult to make a definitive diagnosis. In such instances, a thorough examination is crucial. The main aim of an examination is to rule in, or out, the relevant neural pathways related to the patient’s history.4
They recommend an evaluation of tone, strength, reflexes, sensation, and vasomotor/ sudomotor activity using a paperclip or pin to test pinprick sensation, a cotton ball, or fingers to test light touch, a reflex hammer cooled with tap water to test response to cold, a tuning fork at 128Hz for vibration sensation and a thermometer to assess vasomotor responses.4
Sensory changes should be rated as increased, decreased or normal. A patient with NP generally demonstrates decreased sensation to some sensory modalities and report pain in response to others.4
If a neural lesion is suspected, the authors recommend an electroneuromyography and a nerve stimulation study. These can be used to improve the definition of the affected region/area.4
Step 4: Refer for specialised care or initiate treatment
Should the examination fail to reveal a clear diagnosis, but NP is still suspected, the patient should be referred to a neurologist or a clinician specialising in pain management.4
Bates et al emphasise the importance of multidisciplinary care. The team responsible for the management and treatment of patients with NP should include for example a psychologist, physiotherapist, exercise coach, and a masseuse. Therapy to address issues such as depression, anxiety, pain catastrophising, sleep disturbance or deconditioning, to name but a few should be initiated early in the management plan to improve outcomes.4
The above-mentioned modalities can be trailed alone without pharmacological or interventional strategies but should be limited to a duration of six to eight weeks. If adequate pain relief is not achieved within this time, first-line medications should be initiated, stress Bates et al. 4
Realistic therapy goals for neuropathic pain are:5
» Pain reduction by ≥30%
» Improvement of sleep quality
» Improvement of quality of life
» Preservation of social activity and relationships
» Maintaining the ability to work
» Improved functionality.
Bates et al caution that before initiating treatment, potential side effects and possible drug-drug interactions should be considered – especially in patients with comorbidities. For instance, in patients with diabetic neuropathy, poor glycaemic control worsens symptoms and by improving glycaemic control may reduce progression of neuropathy.4
HIV-associated neuropathy presents an even more complex picture. Starting antiretrovirals may initially improve symptoms although nerve damage may progress. Some antiretrovirals can cause neuropathy, and neurotoxicity may also be a feature of concomitant medicines such as isoniazid in patients co-infected with tuberculosis.4
According to the authors of the 2020 German guideline on the management of NP, ‘gabapentin and pregabalin shall be used as preferred first choice for the management of chronic NP of any aetiology’.5
The 2020 National Institute for Health and Care Excellence guidance recommend that all NP (except trigeminal neuralgia) should be treated with either amitriptyline, duloxetine, gabapentin or pregabalin as initial treatment. Carbamazepine is recommended as initial treatment for trigeminal neuralgia.6
The 2018 South African guideline recommends four classes of agents for use in the treatment of NP: Gabapentinoids (pregabalin and gabapentin), tricyclic antidepressants (TCA), serotonin and noradrenaline reuptake inhibitors (SNRI) and opioids.7
For the treatment of peripheral NP, firstline therapy consists of oral monotherapy using a pregabalin or gabapentin, a low-dose TCA (amitriptyline) or a SNRI (duloxetine or venlafaxine). Pregabalin is usually the agent of choice. Central NP is often difficult to treat but responds to similar treatment. 7
Bates et al recommend a three- to eightweek trial. The efficacy of the prescribed treatment should be reviewed midway and at the end of the trial.4
If the patient does not receive significant relief or has adverse effects from medication, then dosing should be adjusted, an alternative medication or combination therapy should be tried, or the patient should be considered for a trial of neurostimulation.4
How effective are gabapentanoids?
Gabapentin and pregabalin are anticonvulsant medications that act by blocking presynaptic alpha-2-delta calcium channels in the dorsal horn, inhibiting neurotransmitter release.4,5
Gabapentin and pregabalin both have been shown to be effective in post-herpetic neuralgia and diabetic peripheral neuropathy. Pregabalin also has been shown to be superior to placebo in the treatment of spinal cord injury.4
A Cochrane review of gabapentin for chronic neuropathic pain in adults confirmed that gabapentin is associated with greater rates of pain relief compared with placebo in post-herpetic neuralgia and diabetic peripheral neuropathy.4,5
Finnerup et al also assessed the efficacy of pregabalin. The combined number-neededto-treat of 25 randomised controlled trials was 7.7, and the number-needed-to-harm was 13.9. Unlike gabapentin, they also reported a dose response, with a greater response being seen in those taking 600mg daily than in those taking 300mg. Pregabalin has also been shown to decrease health care and non–health care costs compared with gabapentin in the treatment of peripheral NP.4,5
Bates et al recommend that gabapentanoids should be trialled for a four- to six-week period with two weeks at the maximum tolerated dose. Poorly tolerated side effects or inadequate pain relief should prompt dosage adjustment, cessation of the medication, progression to other firstline agents, or a trial of combination therapy. The most common adverse effects include somnolence, fatigue, dizziness, and lower extremity oedema.4
Conclusion
NP negatively impacts patient’s and caregivers’ QoL. It is a debilitating condition, difficult to diagnose, and can only partially responsive to treatment. A multidisciplinary, structured stepwise approach is needed to decrease pain and attain an acceptable QoL for patients. First-line pharmacotherapy includes gabapentin and pregabalin.
References
1. Murnion BP. Neuropathic pain: current definition and review of drug treatment. Aust Prescr, 2018.
2. Machado-Duque ME, Gaviria-Mendoza A, Machado-Alba JE and Castano N. Evaluation of Treatment Patterns and Direct Costs Associated with the Management of Neuropathic Pain. Pain Research and Management, 2020.
3. Finnerup NB, Kuner R ad Jensen TS. Neuropathic Pain: From Mechanisms to Treatment. Physiological Reviews, 2020.
4. Bates D, Schulteis BC, Hanes MC et al. A Comprehensive Algorithm for Management of Neuropathic Pain. Pain Medicine, 2019.
5. Schlereth T et al. Guideline diagnosis and noninterventional therapy of neuropathic pain of the German Society of Neurology (deutsche Gesellschaft für Neurologie). Neurological Research and Practice, 2020.
6. NICE. Neuropathic pain – pharmacological management The pharmacological management of neuropathic pain in adults in non-specialist settings. https://www.nice.org.uk/guidance/cg173/ evidence/full-guideline-pdf-4840898221
7. Patel S. Guidelines for the treatment of neuropathic pain in South Africa. SAMJ, 2018. SF
To complete this month’s CPD questionnaire, please go to www.medicalacademic.co.za and navigate to the CPD section of the website.
