Pharmacological Management of Neuropathic Pain

• Neuropathic low back pain and neck pain affect about 7-8% of the world’s adult population.
• It is a leading cause of occupational disability and results in a significant economic burden.
• Neuropathic pain does not respond to conventional analgesics and anti-inflammatory drugs.
• Pharmacological agents like tricyclic antidepressants, gabapentin, pregabalin and serotonin-norepinephrine reuptake inhibitors (SNRIs) have been found the most beneficial in pain management.

Neuropathic pain in the neck and lower back affects around 7-8% of the adult population and leads to loss of a significant number of workdays. It does not respond to common analgesics and anti-inflammatory drugs. A recent article in the US Pharmacist reviewed the treatment options available and provided recommendations. Neuropathic pain is chronic pain caused due to damage to the nervous system. It may be accompanied by damage to the nerve fibers as well. Neuropathic pain may be associated with tingling, numbness or a burning sensation which spreads along the route of the nerve. While neuropathic pain is described as a ‘sharp, stabbing’ pain, musculoskeletal pain is ‘dull and aching’ in nature.

As mentioned earlier, common analgesics do not provide relief in case of neuropathic pain. Practice guidelines issued by American College of Physicians and American Pain Society indicate evidence in support of non-pharmacological treatments for chronic back pain such as yoga, acupuncture and physical therapy but little evidence exists to prove their efficacy in neuropathic pain.

First Line of Treatment

The preferable and most accepted treatment regimen or first line of treatment of neuropathic pain is as follows:

1. Tricyclic Antidepressants (TCA) like amitriptyline, desipramine and nortriptyline relieve neuropathic pain in both normal as well as depressed individuals. TCAs are beneficial in pain-related insomnia (lack of sleep) too. They are well tolerated and therefore are the first choice of treatment.
   
   
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   Associated side effects of TCAs may be drowsiness, dizziness, dry mouth and general weakness.
2. Anticonvulsants / Gaba Analogs:
   
   Gabapentin and pregabalin are anticonvulsants which have been found efficacious in the management of various neuropathic pain syndromes and can be used as the first choice of treatment in patients in whom TCAs are contraindicated.
   
   
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   The side-effects that may occur with their use are constipation, dry mouth, nausea, headache, and loss of balance.
3. Serotonin-norepinephrine reuptake inhibitors (SNRIs) - Duloxetine and venlafaxine are SNRIs which provide relief in nerve-related pain and are also useful in treating concomitant depression.
   
   Drowsiness, dizziness, dry mouth, and nausea are some of the side-effects that may be observed with their use.

Second Line of Treatment

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When the first line of treatment does not work or its use is limited due to side-effects, the second line of treatment is used in the form of tramadol. Several trials have shown that tramadol provides effective symptomatic relief in neuropathic pain.

Other options include topical agents like capsaicin and lidocaine patches. Lidocaine patch(5%) can be used for pain relief in patients who are unable to tolerate oral drugs due to side-effects. Lidocaine acts as a local anesthetic agent and provides short-term relief from pain.

Capsaicin patch (8%) can be used topically but may result in a rise in blood pressure. It may also cause burning and irritation at the site of application unless ice is applied.

Third Line of Treatment

Opioids like morphine are given the least preference in the treatment of neuropathic pain and remain as third line therapy and can provide further relief when used in conjunction with gabapentin. Their propensity to cause dependence is a major deterrent to their use.

The property of botulinum toxin A to inhibit both the secretion of inflammatory mediators and the release of neurotransmitters from nerve fibers is utilized for pain relief through subcutaneous injections of the toxin.

The general rule to be applied in the clinical management of neuropathic pain is the use of a single drug at a time. The transition from starting dose to target dose must be titrated and patient safety must be kept in mind. In case a drug does not produce desired effects, a combination of two may be tried. It is important to keep the patient’s medical history, age, and comorbidities in consideration while deciding on the line of treatment.

Certain other agents are also being researched for the management of neuropathic pain. One of these involves mutation of SCN9A, which blocks the pain signals that are carried by the nerve cells. The loss of pain sensation is mainly due to the blockage of voltage gated sodium channels (NaV)1.7 Studies are also under way to research an agent which is associated with nitric oxide production in neuropathic pain. Inhibition of nitric oxide production may result in pain relief.

Owing to the various factors and complexities involved in the management of neuropathic pain, it may be advisable to use a multidisciplinary approach involving the use of pharmacological therapy as well as alternative treatments like physiotherapy, rehabilitation, support groups and behavioral therapy. Pharmacological therapy would still remain the mainstay of treatment. However, informed decisions regarding treatment must be made according to the patient’s characteristics and comorbidities.

Source-Medindia