Is Amitriptyline Good for Nerve Pain?

Nerve pain, or neuropathic pain, can be debilitating. Among the various treatments available, amitriptyline, a medication primarily known as an antidepressant, has been shown to be good for reducing nerve pain. But how effective is it really? In this post, i'll explain why by looking at its mechanism and several studies.

Jim Hollyhead

1/10/20255 min read

Is Amitriptyline Good for Nerve Pain?

What is Nerve Pain?

Nerve pain - also known as neuropathic pain - is caused by damage to the somatosensory system. This is a collection of nerve pathways that enables us to interpret sensations such as touch, pressure etc, and is damaged either through disease or physical injury. The pain associated with this type of damage can be debilitating, and typical symptoms include: burning, numbness, tingling, shooting, stabbing, or electric-shock-like sensations.

Traditional painkillers such as ibuprofen or paracetamol are usually ineffective sy reducing neuropathic pain. Instead, your health care provider would usually consider prescribing you neuropathic medications. One of which is Amitriptyline.

What is Amitriptyline?

Amitriptyline is a tricyclic antidepressant - referring to the chemical composition of the medication - and was first approved for clinical use in 1961. It is indicated to treat depression, emotional lability in multiple sclerosis, recalcitrant abdominal pain and neuropathic pain.

How Does Amitriptyline Work For Nerve Pain?

Amitriptyline’s mechanism for reducing neuropathic pain are well studies, and include multiple pharmacologic actions (more on that here):

  • Modulation of Neurotransmitters: amitriptyline works by inhibiting the reuptake of two neurotransmitters: serotonin and norepinephrine, in the brain and spinal cord. These two neurotransmitters are involved in modulating pain, amongst other functions and by increasing their concentration within the synaptic cleft this enhances the descending pain inhibitory pathways. Thes are a network of neurons that originate in specific brain regions, such as the periaqueductal gray and the rostral ventromedial medulla (RVM) and extend down to the spinal cord. They work by reducing but do not entirely block, pain signals from the peripheral nerves from reaching the brain via the spinal cord.

  • Sodium Channel Blockade: amitriptyline blocks use-dependent sodium channels in nerve membranes, reducing the excitability of peripheral nerves. The influx of sodium is imperative for generating action potentials - essentially, an electric signal - to convey pain signals from the damaged nerve to the brain. When nerves are damaged this leads to an increased accumulation and overactivity of sodium channels at the injury site which leads to excessive firing of pain signals. Amitriptyline binds to sodium channels and stabilises them in an inactivated state, which reduces the firing of damaged nerves and therefore fewer pain signals are sent to the spinal cord and brain leading to a lower perception of pain.

  • N-methyl-D-aspartate (NMDA) receptor inhibition: NDMA receptors are glutamate-gated ion channel gated - meaning they are activated by glutamate - found on neurons and are involved in, amongst others, pain transmission; specifically, they become hyperexcitable which amplifies nerve signalling when a nerve is damaged. Amitriptyline binds to this receptor and prevents ion influx - specifically calcium and sodium - preventing neuronal hyperexcitability and reducing pain signals.

What types of nerve pain can amitriptyline treat?

As mentioned earlier, Amitriptyline is indicated to treat neuropathic pain, of which there are several types, including:

  • Diabetic neuropathy: a condition affecting up to 30% of diabetic patients and arises from long-term damage to peripheral nerves from high blood sugar – known as hyperglycaemia. It most commonly manifests in the feet and symptoms include burning, tingling and numbness, which are often worse at night.

  • Postherpetic Neuralgia: chronic nerve pain following an outbreak of shingles. It affects up to 20% of people with shingles, and symptoms include burning, lancinating pain and stabbing-type pain in areas affected by shingles rashes.

  • Trigeminal Neuralgia: a painful condition affecting the face, that arises from irritation or compression to the trigeminal nerve. Symptoms include severe electric-shock type pain that are worsened by chewing or touching the face.

  • Spinal Cord Injury – neuropathic pain occurs in up to 60% of patients with spinal cord injuries, and pain can manifest at the level of the injury or below. Symptoms include tingling, burning and electric-shock-type sensations.

  • Central post-stroke pain – a condition affecting up to 20% of stroke patients, that occurs due to damage within the central pain process pathways areas of the brain such as the thalamus. Symptoms include burning, tingling and aching.

What is the evidence for amitriptyline's effectiveness?

Numerous studies support the use of amitriptyline for nerve pain for certain neuropathic pain conditions such as diabetic neuropathy and postherpetic neuralgia, whilst results are inconsistent for others such as neuropathic pain caused by spinal cord injury-related neuropathic pain:

  • Max et al. (1992) conducted a randomised double blind crossover trial of 29 participants with diabetic neuropathy. They found Amitriptyline significantly reduced pain intensity compared to placebo (p < 0.05), with 74% of participants reporting at least moderate pain relief. Similar efficacy to desipramine but superior to fluoxetine. The double blinding reduced the risk of bias, however the small sample size limits this study’s generalisability.

  • Moore et al (2015): conducted systematic review of randomised controlled trials in assessing Amitriptyline’s efficacy for chronic neuropathic pain in adults with condition including diabetic neuropathy, postherpetic neuralgia, spinal cord injury and others. The found Amitriptyline effective for diabetic neuropathy and postherpetic neuralgia, but limited efficacy for spinal cord injury neuropathic pain and HIV related neuropathy. Despite these findings and some studies using rigorous methodology, much of the evidence was of low quality with small sample sizes, and only two of the seven studies were placebo controlled.

  • Cardenas et al. (2002) conducted a randomised double-blind placebo-controlled trial on 84 participants with spinal cord injury. They found no significant difference in pain scores between amitriptyline and placebo. Despite being a well-controlled trial with a large sample size, the inclusion of non-neuropathic pain diluted the neuropathic pain findings.

  • Graff-Radford et al (2000) – conducted a randomised, double-blind placebo-controlled trial of 49 participants with postherpetic neuralgia. They found Amitriptyline significantly reduced pain intensity compared to placebo, with 55% of the participants reporting moderate pain relief. This was a well-controlled study, but the small sample limits its generalisability.

Conclusion

As shown in the studies above, Amitriptyline can be a good medication choice to help reduce certain types of neuropathic pain such as diabetic neuropathy and postherpetic neuralgia. But, as with all medications, despite their efficacy they often come with side effects such as dry mouth, constipation and sedation which may be unpalatable for many patients. Some of these side effects may be dose dependent, while others may be person-specific, and your decision to proceed with Amitriptyline should come after a thorough discussion around the risks and side effects of prescribing such medication.

If you are suffering with nerve pain, you can consult with me here.

References

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