Nerve Pain — Causes, Symptoms, Diagnosis & Treatment Guide — Symptoms, Causes & Treatment | MyMedicPlus

Nerve pain (neuropathic pain) arises from damage or dysfunction of the somatosensory nervous system rather than from tissue injury. It affects 7-10% of the population and is a major contributor to chronic pain disability. Unlike nociceptive pain (from tissue damage), neuropathic pain persists beyond normal healing time and is often described as burning, shooting, stabbing, or electric shock-like in quality. Neuropathic pain is distinguished from nociceptive pain (from tissue injury) by its characteristic quality descriptors, its persistence beyond normal healing time, and its failure to respond to standard analgesics. It affects 7-10% of the general population — representing approximately 550 million people globally — and is one of the most burdensome and treatment-resistant pain conditions. Neuropathic pain arises when either the peripheral nervous system (peripheral neuropathic pain — from nerve damage in the periphery) or the central nervous system (central sensitisation — from spinal cord or brain pathology) is damaged or dysfunctional, generating ectopic electrical discharges from injured neurons and aberrant central pain processing. The NeuPSIG grading system (possible, probable, definite) grades diagnostic certainty based on the clinical and neurophysiological evidence. Common specific syndromes include diabetic peripheral neuropathy (affecting 50% of diabetics with greater than 10 years disease duration), post-herpetic neuralgia (developing after shingles in 10-20% of patients over 60), and lumbar radiculopathy.

Peripheral causes: diabetic peripheral neuropathy (most common in developed countries), post-herpetic neuralgia (following shingles), trigeminal neuralgia, carpal tunnel syndrome, chemotherapy-induced neuropathy, HIV-associated neuropathy, and radiculopathy from disc herniation. Central causes: post-stroke central pain, multiple sclerosis, and spinal cord injury pain. Metabolic causes include diabetes mellitus, hypothyroidism, and vitamin B12 deficiency. Peripheral neuropathic pain mechanisms include: ectopic neuronal discharge from injured afferent neurons with altered sodium channel expression (Nav1.7, Nav1.8 upregulation); spontaneous discharge from neuroma formation; central sensitisation from windup and long-term potentiation (AMPA and NMDA receptor-mediated); and loss of inhibitory control from damaged inhibitory interneurons and descending inhibitory pathways (noradrenergic and serotonergic). Specific mechanism-cause correlations: Nav1.7 gain-of-function mutations cause inherited erythromelalgia (burning extremity pain) and paroxysmal extreme pain disorder. TRPV1 receptor sensitisation explains heat allodynia in post-herpetic neuralgia — the basis for capsaicin 8% patch (TRPV1 desensitisation). In diabetic neuropathy, advanced glycation end-products (AGEs) damage Schwann cells, blood-nerve barrier endothelium, and axon mitochondria through oxidative stress and microangiopathy. Chemotherapy-induced peripheral neuropathy (CIPN) from platinum compounds (oxaliplatin, cisplatin), taxanes (paclitaxel, docetaxel), and vinca alkaloids (vincristine) damages dorsal root ganglion neurons.

Characteristic descriptors include burning, shooting, electric shock-like, stabbing, and tingling (paraesthesia). Allodynia (pain from normally non-painful stimuli such as light touch or clothing) and hyperalgesia (exaggerated pain response) are hallmarks. Spontaneous pain without any trigger, pain worse at night disrupting sleep, and autonomic features (skin color/temperature changes) are common. Negative symptoms include numbness and sensory loss. Positive sensory symptoms — spontaneous or stimulus-evoked abnormal sensations — are characteristic of neuropathic pain. Spontaneous symptoms: constant burning pain (most common — described as 'like fire on the skin' or 'immersed in boiling water'); paroxysmal shooting, electric shock-like, or stabbing pain lasting seconds; and dysaesthesia (unpleasant abnormal sensations without pain, like crawling, tingling, or pressure). Stimulus-evoked symptoms: allodynia (pain from a normally non-painful stimulus — clothing contact, light touch, temperature change — present in 30-50% of neuropathic pain patients); hyperalgesia (exaggerated response to a mildly painful stimulus); and temporal summation (increasing pain to repeated identical stimuli — 'wind-up'). Negative sensory symptoms — sensory loss from nerve damage — include numbness, reduced vibration sense, proprioceptive loss (causing gait ataxia and falls), and reduced temperature perception (leading to burns and ulcers in diabetic neuropathy). Sleep disturbance from nocturnal worsening is reported by 70% of patients.

Validated screening tools: DN4 questionnaire (sensitivity 83%, specificity 90%) and LANSS scale identify neuropathic components. Neurological examination assesses sensory modalities (pinprick, temperature, vibration, joint position) to identify sensory loss patterns. Nerve conduction studies and EMG define large-fiber neuropathy. Skin punch biopsy (intraepidermal nerve fiber density) is the gold standard for small-fiber neuropathy. MRI identifies structural lesions. The DN4 questionnaire (Douleur Neuropathique en 4 questions) scores 0-10 — a score above 4 has 83% sensitivity and 90% specificity for neuropathic pain; the LANSS (Leeds Assessment of Neuropathic Symptoms and Signs) similarly identifies neuropathic components with embedded bedside sensory examination. Quantitative sensory testing (QST) characterises the sensory profile — detecting loss of thermal (warm/cold) and mechanical detection thresholds, hyperalgesia, and allodynia — important for research and in defining pain mechanism phenotype. Nerve conduction studies (NCS) and electromyography (EMG) identify large fibre neuropathy (demyelinating vs axonal; motor vs sensory vs mixed) — normal in small fibre neuropathy. Skin punch biopsy at the distal leg — immunohistochemical staining for PGP9.5 (pan-neuronal marker) — counts intraepidermal nerve fibre (IENF) density; IENF density below the 5th percentile for age and sex confirms small fibre neuropathy with high specificity. Autonomic function testing (cardiovascular reflex tests, sweat testing) for autonomic neuropathy. Blood investigations for secondary causes: HbA1c, fasting glucose, vitamin B12, folate, TSH, renal function, serum immunoglobulins with electrophoresis (MGUS), HIV, hepatitis B and C, and vasculitis screen (ANCA, complement, ANA).

First-line: gabapentin or pregabalin (calcium channel alpha-2-delta ligands), duloxetine or venlafaxine (SNRIs), and tricyclic antidepressants (amitriptyline, nortriptyline). Topical therapies: lidocaine 5% patches (post-herpetic neuralgia), capsaicin 8% patch (TRPV1 desensitization, single application). Second-line: tramadol, opioids (for severe refractory pain with careful monitoring). Interventional: nerve blocks, spinal cord stimulation for refractory cases. Treat underlying cause (glycemic control for diabetic neuropathy). Combination pharmacotherapy is often required as no single agent reliably provides greater than 50% pain relief in all patients. Tricyclic antidepressants (amitriptyline 10-75 mg at night; nortriptyline for better tolerability) provide NNT of approximately 2.5 for neuropathic pain — oldest but most evidence-based class; side effects (dry mouth, constipation, urinary retention, sedation, cardiac effects) limit use particularly in elderly. Gabapentinoids: gabapentin 300-3600 mg/day in divided doses (NNT approximately 6 for diabetic neuropathy); pregabalin 150-600 mg/day (NNT approximately 4; FDA-approved for multiple neuropathic indications) — both work via calcium channel alpha-2-delta subunit; CNS effects (dizziness, sedation, peripheral oedema) and risk of misuse/dependence require caution. SNRIs: duloxetine 60-120 mg/day (FDA-approved for diabetic peripheral neuropathy and fibromyalgia; NNT approximately 5) and venlafaxine 150-225 mg/day — preferred over TCAs in elderly patients. Capsaicin 8% patch (Qutenza) for post-herpetic neuralgia and HIV neuropathy — applied by a trained healthcare professional for 30-60 minutes; provides approximately 50% pain relief for 8-12 weeks in 30-40% of patients through TRPV1 desensitisation. Lidocaine 5% medicated plasters for post-herpetic neuralgia with allodynia.

Chronic neuropathic pain causes significant quality-of-life impairment: sleep disturbance (in 70%), depression and anxiety, reduced physical function and mobility, and social isolation. In diabetic neuropathy, sensory loss increases fall risk and foot ulcer risk leading to amputation. Analgesic dependence and opioid misuse are risks with long-term opioid prescribing. Post-herpetic neuralgia can persist for years causing severe disability. Sleep disruption — the most universally reported complication — affects up to 70% of neuropathic pain patients; non-restorative sleep from pain arousals causes daytime fatigue, impairs cognitive function, and lowers pain threshold in a cycle perpetuating the pain experience. Depression and anxiety are bidirectionally related to neuropathic pain — depression is present in 40-60% of patients with chronic neuropathic pain, significantly worsening pain intensity scores and quality of life. In diabetic peripheral neuropathy, sensory loss (particularly loss of protective sensation — absent 10g monofilament response) dramatically increases foot ulcer risk: the lifetime risk of a diabetic foot ulcer is 15-25%, with ulcers leading to amputation in 20% of cases; diabetic neuropathy is the leading cause of non-traumatic lower limb amputation globally. Analgesic dependence and misuse: opioids prescribed for refractory neuropathic pain carry addiction risk; gabapentinoids (particularly pregabalin) are increasingly misused and diverted — classified as Schedule 3 controlled drugs in the UK since 2019. Falls and hip fractures from proprioceptive loss, muscle weakness, and sedating medications are significantly more common in neuropathic pain patients. Marked reduction in functional capacity — inability to work, drive, exercise, or engage in social activities — causes significant economic and social burden.

For diabetic neuropathy prevention: maintain HbA1c below 7%, monitor feet daily for ulcers, and use SGLT2 inhibitors or GLP-1 agonists that have neuroprotective effects. Shingles vaccination (recombinant zoster vaccine, RZV) reduces both shingles incidence and post-herpetic neuralgia by 90%. Prompt antiviral treatment (aciclovir within 72 hours of shingles rash) reduces PHN risk. Chemotherapy dose modification where possible reduces CIPN severity. The most impactful prevention strategy is rigorous glycaemic control in diabetes — the DCCT trial demonstrated that intensive insulin therapy reducing HbA1c from 9% to 7% reduced the incidence of diabetic peripheral neuropathy by 60% in Type 1 diabetes over 5 years; UKPDS shows similar (but less dramatic) benefit in Type 2 diabetes. Recombinant zoster vaccine (Shingrix/RZV) prevents shingles — the cause of post-herpetic neuralgia — with 97% efficacy in adults aged 50-69 and 91% in those aged 70 and above; two doses given 2-6 months apart; strongly recommended for all adults aged 50 and above. Early antiviral treatment of shingles with aciclovir 800 mg 5 times daily within 72 hours of rash onset reduces acute neuritis severity and reduces PHN development by 20-50%. CIPN prevention: dose modification of neurotoxic chemotherapy based on cumulative toxicity monitoring; calcium and magnesium infusions reduce oxaliplatin CIPN in some studies; cryotherapy (cooling gloves and socks) during infusion reduces taxane and platinum CIPN. Vitamin B12 deficiency neuropathy is fully preventable with B12 supplementation — monitor B12 in patients on long-term metformin (impairs B12 absorption).

See your GP for: burning, shooting, stabbing, or electric shock-like pain persisting for more than 4-6 weeks; pain associated with numbness or tingling not explained by a simple cause; pain that is keeping you awake at night or preventing normal daily activities; or painful sensations from light touch or temperature that should not normally be painful (allodynia). Seek urgent GP or neurology assessment for: rapidly progressive sensory loss or muscle weakness (possible myelopathy or rapidly progressive neuropathy), new neurological symptoms in a patient with known diabetes (diabetic neuropathy can progress rapidly and cause foot ulcers if undetected), or severe post-shingles pain developing in immunocompromised patients (early recognition of PHN allows earlier treatment). Go to A&E immediately for: sudden onset severe pain with new lower limb weakness, loss of bladder or bowel control, or saddle anaesthesia (cauda equina syndrome — a surgical emergency requiring emergency MRI within hours); or any rapidly progressive neurological deficit with neuropathic pain. Report any worsening of neuropathic pain in diabetic patients to your GP promptly — deterioration indicates poor glycaemic control requiring urgent review.