Neuropathic pain and spasticity

• Neuropathic pain is pain caused by a lesion or disease of the somatosensory nervous system — the system that carries touch, temperature, pain and position sense. It is a different problem from ordinary (nociceptive) pain, and it responds to different drugs. ^[3]
• The IASP definition is the current standard, and the condition is graded "possible", "probable" or "definite" according to how much evidence there is for nerve damage.
• It is common: up to 10% of people experience neuropathic pain, and in one systematic review the prevalence in the general population ranges from 6.9 to 10%.^[4]
• First-line drugs for neuropathic pain (except trigeminal neuralgia) are a choice of amitriptyline, duloxetine, gabapentin or pregabalin; if one fails, switch to one of the other three.^[1]
• Trigeminal neuralgia is treated first with carbamazepine; postherpetic neuralgia is treated with the same first-line group plus topical agents.
• Spasticity is not neuropathic pain. It is velocity-dependent muscle overactivity after damage to the central nervous system; focal spasticity is treated with botulinum toxin, and more widespread spasticity with oral agents such as baclofen and tizanidine.^[7][8][9]

By the end of this page you should be able to:

1. Define neuropathic pain and distinguish it from nociceptive pain, giving typical symptoms and sensory signs.
2. Grade a patient's pain as possible, probable or definite neuropathic pain using the NeuPSIG criteria.
3. Choose and titrate a first-line drug for neuropathic pain, and state which drugs NICE advises against starting in non-specialist practice.
4. Recognise and manage trigeminal neuralgia and postherpetic neuralgia.
5. Plan treatment of spasticity, matching the pattern of muscle overactivity to baclofen, tizanidine or botulinum toxin, with safe dosing and withdrawal precautions.
6. Describe when to refer, and what to do in low-resource settings.

Neuropathic pain differs from nociceptive pain, which is pain arising from actual or threatened tissue damage in non-neural tissue, such as a cut, a fracture or an inflamed joint. The distinction matters because the two types of pain are assessed and treated differently: opioids and conventional analgesics are not targeted treatments for neuropathic pain, whereas gabapentinoids, tricyclic antidepressants and serotonin–noradrenaline reuptake inhibitors are evidence-based first-line choices, and NSAIDs have no proven efficacy against neuropathic pain.^[4]

Neuropathic pain may be peripheral (from damage to a cranial nerve, a peripheral nerve, a nerve root or the sensory fibres of a polyneuropathy) or central (from damage to the spinal cord, brainstem or brain, as after stroke, spinal cord injury or multiple sclerosis). Mixed pictures are common, for example painful radiculopathy in the leg with back pain, or cancer pain with nerve infiltration. Patients often have both neuropathic and nociceptive pain at once, and both may need treatment.^[3][4]

The common causes are a useful memory map:

• Peripheral: trigeminal neuralgia; postherpetic neuralgia; painful diabetic polyneuropathy (up to 30% of people with type 2 diabetes^[4]); post-traumatic or post-surgical nerve injury; chemotherapy-induced neuropathy; HIV-associated neuropathy; post-amputation pain.
• Central: central post-stroke pain; spinal cord injury pain; pain associated with multiple sclerosis.

Pain that is "primarily related to spasticity" should be classified as musculoskeletal pain, not neuropathic pain, and managed as spasticity.^[4]

Spasticity is a separate entity. It is a velocity-dependent increase in muscle tone due to damage to the central nervous system, part of the upper motor neurone syndrome. It is not defined by pain. Pain associated with spasticity is secondary: it can come from muscle overactivity, awkward posture, contracture or skin breakdown. Treating the spasticity, the pain, and the cause of each must be planned separately.^[7]

Neuropathic pain is common and often under-treated. Up to 10% of the general population experience neuropathic pain, and a systematic review cited in the IASP/ICD-11 classification found a prevalence between 6.9 and 10%.^[4] Estimates vary because studies use different definitions, and many surveys detect "pain with neuropathic characteristics" rather than clinically graded neuropathic pain.

The condition is more common in groups who suffer the diseases that cause it:

• As many as 20% of patients with herpes zoster develop postherpetic neuralgia.^[6]
• Approximately half of all postherpetic neuralgia cases occur in people older than 60 years.^[6]
• Painful diabetic polyneuropathy affects a large minority of people with diabetes.
• Central post-stroke pain and spinal-cord-injury pain affect substantial minorities of survivors.

Chronic neuropathic pain causes more suffering and disability than its underlying disease in many patients, and the majority of patients do not get satisfactory relief from first-line drugs.^[4]

The cause is always a lesion or disease of the somatosensory system, and the pain usually persists after the acute injury has healed. Recognised causes include trauma (nerve injury, surgery, amputation), infection (herpes zoster), metabolic disease (diabetes mellitus), vascular disease (stroke), autoimmune and inflammatory disease (multiple sclerosis, vasculitis), neurodegenerative disease, tumour (compression or infiltration), exposure to toxins (chemotherapy, alcohol), and hereditary channelopathies. In some patients the cause is never found.

Risk factors for developing neuropathic pain after a known nerve lesion include older age, more severe acute pain, more severe or more extensive initial injury, and diabetes. In herpes zoster, severe acute zoster and a notable prodrome are associated with higher risk of postherpetic neuralgia.^[6]

There is no known lifestyle risk factor and no primary prevention for most neuropathic pain. The important prevention targets are the underlying diseases: good glycaemic control in diabetes, vaccination against varicella zoster where available, and injury prevention.

The pain is generated by the damaged nervous system itself, not by the injured tissue. Several mechanisms act together:

1. Ectopic activity. Damaged or regenerating nerve fibres gain inappropriate pacemaker activity and fire spontaneously. Injured A-fibres and C-fibres sprout and form new connections that amplify any signal.
2. Peripheral sensitisation. Inflammation around an injured nerve increases the number and sensitivity of ion channels (especially sodium channels) in nociceptors, lowering their firing threshold.
3. Central sensitisation. Sustained nociceptive input reorganises synapses in the dorsal horn of the spinal cord and higher brain centres. Excitatory transmission is enhanced, and inhibitory control is weakened. This produces allodynia and hyperalgesia.
4. Deafferentation and reorganisation. Loss of normal sensory input causes surviving fibres and cortical circuits to reorganise. Abnormal connections can produce pain in an area that has lost sensation — the classic "anaesthesia dolorosa".
5. Loss of inhibition. Descending pain-inhibitory pathways from the brainstem and cortex lose their braking effect after nerve injury and central disease.

These mechanisms explain why neuropathic pain is often described as burning, shooting, electric shock-like or stabbing, why it can be triggered by light touch (allodynia), and why it is poorly relieved by drugs that work on tissue inflammation.

Patients rarely say they have neuropathic pain. Useful questions focus on the words they use and the distribution:

• Quality: burning, shooting, electric shock, stabbing, pricking, pins and needles, numbness. The combination of several descriptors increases the likelihood of neuropathic pain.
• Negative symptoms: numbness, deadness, reduced sensation.
• Evoked pain: allodynia (pain from light touch), hyperalgesia, cold-induced pain.
• Distribution: a dermatomal band, a peripheral nerve territory, a glove-and-stocking area, or a central pattern after stroke or spinal cord injury. The distribution should be neuroanatomically plausible.
• Temporal relationship: pain develops within days or weeks after a nerve lesion, although it may be delayed for months (after stroke) or for years (as in slowly progressive polyneuropathy). Pain can also be the only manifestation of disease, as in trigeminal neuralgia.
• Functional impact: sleep disturbance is frequent and is an explicit target of treatment.

Screening questionnaires such as DN4, painDETECT and LANSS structure this part of the assessment and alert the clinician to possible neuropathic pain. They are helpful in identifying patients who need further assessment, but they do not diagnose neuropathic pain on their own.^{[3] [2]}

A focused neurological examination compares the painful area with a mirror or nearby non-painful area, looking for:

• Negative sensory signs: reduced light touch, pinprick, temperature (cold, warm), vibration, position sense.
• Positive sensory signs: allodynia (light touch, cold or brush), hyperalgesia, wind-up.
• Motor or autonomic signs in the same distribution, depending on the lesion.

Compare both sides. In nerve entrapment or focal neuropathy, signs are confined to the nerve territory; in polyneuropathy they are distal and symmetric; in central pain they follow the lesion's somatotopic distribution. Because neuropathic pain can be episodic, sensory abnormalities may not be detectable at the time of examination.^[3]

The NeuPSIG grading system rates how certain it is that the pain is neuropathic.^[3][4]

"Probable" is usually enough to start treatment according to neuropathic pain guidelines. "Definite" is useful in specialist contexts or when treating the underlying cause is possible. Not all pain in an area of nerve damage is neuropathic — a patient with spinal cord injury may have shoulder pain from a rotator cuff problem, or spasticity-related pain below the level of injury.^[3][4]

Spasticity is assessed by a trained clinician, usually as part of a rehabilitation team, because it affects movement, posture and function:

• Velocity-dependent increase in tone on passive stretch, with the "clasp-knife" quality.
• Clonus, hyperreflexia, positive Babinski sign and mass synergy patterns (positive features of the upper motor neurone syndrome).
• Negative features: weakness, loss of dexterity, fatigue.
• Severity scales such as the Modified Ashworth Scale and Tardieu scale are commonly used in practice and research, though they have well-known limitations.
• Functional assessment, pain, posture, skin integrity and carer burden.

The pattern matters more than the score: focal (one or two muscles), segmental (limb or part of a limb) or widespread (multiple body regions). The pattern determines the drug strategy.^[7]

Two questions arise in neuropathic pain: what could be causing nerve damage, and what else could the pain be. The main mimics and how to separate them are summarised below.

For spasticity itself, the main differential is other causes of hypertonia and movement disorder: dystonia, parkinsonism (rigidity is not velocity-dependent), contracture without overactivity, and clonus on its own. Useful tests are a full neurological examination and, in uncertain cases, assessment in a specialist spasticity clinic.^[7]

Neuropathic pain is a clinical diagnosis, supported by investigation. The investigation chosen follows the suspected site of the lesion.

• Screening questionnaires (DN4, I-DN4, LANSS, S-LANSS, painDETECT) identify patients who may have neuropathic pain and structure the history. They do not diagnose on their own.^{[2] [3]}
• Clinical examination for sensory signs in a plausible distribution.^[3]
• Imaging for structural causes: MRI of the brain for trigeminal neuralgia and central pain; MRI of the spine for radiculopathy and spinal cord disease; MRI of the affected limb where entrapment is suspected.
• Electrophysiology: nerve conduction studies for large-fibre neuropathy; trigeminal reflex testing for secondary trigeminal neuralgia, which is strongly recommended by the EAN/EFIC/IASP.^[2]
• Skin biopsy showing reduced intraepidermal nerve fibre density, used for suspected small-fibre neuropathy; strongly recommended by EAN/EFIC/IASP.^[2]
• Quantitative sensory testing (QST) for somatosensory disturbance; weakly recommended.^[2]
• Nociceptive evoked potentials (laser or contact heat): weakly recommended, a second-line test.^[2]
• Corneal confocal microscopy may be considered for small-fibre damage; no recommendation has been made.^[2]
• Genetic testing in specialist centres for monogenic pain disorders such as erythromelalgia or paroxysmal extreme pain disorder, and for small-fibre neuropathy with a family history.^[2]

For spasticity, investigation aims at the cause (stroke, multiple sclerosis, spinal cord lesion, cerebral palsy, traumatic brain injury) rather than at spasticity itself: brain or spinal imaging, and EMG or electrical stimulation to help localise small or deep muscles before botulinum toxin injection.^[7]

The IASP grading system (possible / probable / definite) is the diagnostic framework above. For trigeminal neuralgia, the ICHD-3 criteria require recurrent paroxysms of unilateral facial pain in the distribution of one or more divisions of the trigeminal nerve, lasting from a fraction of a second to 2 minutes, severe in intensity, electric shock-like, shooting, stabbing or sharp in quality, and precipitated by innocuous stimuli within the affected distribution.^[5]

Severity and impact are measured practically with validated pain-intensity scales, sleep and quality-of-life measures, and neuropathic-specific questionnaires such as Neuropathic Pain Symptom Inventory. For spasticity, severity of hypertonia is graded clinically (for example the Modified Ashworth or Tardieu scales) and, more importantly, functional goals are set with the patient and carers: passive goals (hygiene, dressing, positioning), active goals (gait, hand function) and symptomatic goals (pain, spasm).^[7]

The overall approach is to treat the cause where possible, grade the pain, choose a first-line drug and titrate it, and add or switch drugs stepwise, while involving multidisciplinary care. Urgent referral is needed when red flags are present.

For most neuropathic pain the acute task is assessment, reassurance and starting the right drug, not emergency treatment. Acute severe pain from trigeminal neuralgia can need admission for rehydration and titration — see below. Postherpetic neuralgia in the acute phase of shingles is managed with antivirals and analgesia to shorten the rash and possibly reduce the risk of chronic pain.

For an actual or impending nerve emergency (spinal cord compression, cauda equina, rapidly progressive deficit), manage the underlying emergency first and refer urgently. For spasticity emergencies — autonomic dysreflexia, untreated pain causing autonomic storm, aspiration risk — admit and treat the medical crisis.

NICE CG173 recommends that in non-specialist settings an individualised choice of four first-line drugs is offered for neuropathic pain (except trigeminal neuralgia): amitriptyline, duloxetine, gabapentin or pregabalin.^[1] No single drug has been shown to be superior in any particular syndrome, so the choice depends on comorbidities, contraindications, side-effect profile, convenience and patient preference.^[4]

Key principles from the guideline:^[1]

• Agree a plan with the patient, discussing severity, impact on daily activities and sleep, the underlying cause, the titration process and adverse effects.
• Carry out an early clinical review after starting or changing treatment, then regular reviews of pain control, function, adverse effects and continued need.
• Taper the withdrawal regimen when switching or stopping, to account for dose and discontinuation symptoms.
• Consider referral to a specialist pain service or condition-specific service at any stage — including at first presentation — for severe pain, major functional limitation, or deterioration of the underlying condition.
• Continue an existing effective treatment rather than changing it.

Drugs not to start in non-specialist settings unless a specialist advises (NICE "do not offer" list): cannabis sativa extract, capsaicin patch, lacosamide, lamotrigine, levetiracetam, morphine, oxcarbazepine, topiramate, long-term tramadol, venlafaxine and valproate (with MHRA safety advice for the antiepileptics). Short-term tramadol may be used as acute rescue therapy.^[1]

Topical option. For localised neuropathic pain in people who wish to avoid, or cannot tolerate, oral drugs, consider capsaicin cream 0.075%. NICE notes it was licensed in 2013 for post-herpetic neuralgia and painful diabetic peripheral polyneuropathy only, so its use elsewhere is off-label. The MHRA and NICE also flag that gabapentin and pregabalin are Class C controlled substances (Misuse of Drugs Act 1971, Schedule 3): evaluate for a history of drug abuse before prescribing and watch for abuse and dependence.^[1]

Dosing and titration (practical ranges from sources). Titrate to effect and tolerability, and check local formularies.

• Amitriptyline — a tricyclic antidepressant. Low doses (taken at night and gradually increased) are typically used; in one post-herpetic neuralgia review it was used up to 150 mg/day (multiple daily dosing, variable titration).^[6] Anticholinergic side effects (sedation, dry mouth, constipation, urinary retention, blurred vision) and cardiac toxicity limit use, and the American Geriatrics Society Beers criteria advise avoiding tricyclics in older adults because of these risks. Amitriptyline should be avoided after recent myocardial infarction and in heart block.
• Duloxetine — Duloxetine was licensed in 2013 for diabetic peripheral neuropathic pain only; its use for other neuropathic pain conditions is therefore off-label in the UK.^[1] It is the SNRI of the four and is useful when depression or another chronic pain coexists.
• Gabapentin — licensed in 2013 for peripheral neuropathic pain only.^[1] In post-herpetic neuralgia, immediate-release gabapentin is titrated to an effective maintenance dose, most often 1,800 mg/day or more, in three divided doses; in one review the range used was 1,800–3,600 mg/day. Extended-release and prodrug forms allow simpler once- or twice-daily dosing. Adjust dosing for renal impairment.^[6]
• Pregabalin — 150–600 mg/day in two or three divided doses, with about a one-week titration in licensing studies. Effective for several neuropathic syndromes and also useful for anxiety; sedation, dizziness and weight gain are common. Pregnancy safety advice from the MHRA applies.^[1][6]
• Capsaicin 0.075% cream (Axsain) — applied 3–5 times per day; initial burning is common and the treatment is often reserved for localised pain or oral-drug intolerance.^[6]
• Lidocaine 5% patch — up to three patches per day for localised peripheral neuropathic pain, including post-herpetic neuralgia on the trunk; its patch-based delivery suits dermatomal pain and suits older patients because systemic absorption is low.^[6]

Combination therapy. A single drug rarely controls all of the mechanisms driving neuropathic pain. Combining a gabapentinoid with a tricyclic or a topical agent (for example pregabalin plus lidocaine patch, or gabapentin plus a tricyclic) can improve analgesia; adverse-event rates are no higher than for monotherapy in trials.^[6]

Opioids and others. Opioids provide sedation and analgesia in acute severe pain but are poor long-term treatment for neuropathic pain. NICE lists morphine and long-term tramadol among drugs not to be started for neuropathic pain in non-specialist settings unless a specialist advises it, and cannabis sativa extract is on the same "do not start" list.^[1] Standard practice should therefore follow the NICE first-line pathway rather than cannabis-based products.

Trigeminal neuralgia produces brief (a fraction of a second to about 2 minutes), severe, electric shock-like paroxysms in the distribution of the trigeminal nerve, precipitated by light touch. It is much more common on the right side (about 60%) and usually affects the maxillary and mandibular divisions. Examination is usually normal; around 30% have mild sensory change.^[5]

Manage in non-specialist settings as follows:^[1][5]

• Exclude red flags (constant pain, sensory deficit, bilateral pain, onset in a young person) which point to a secondary cause.
• Take an MRI of the brain as the investigation of choice to exclude secondary trigeminal neuralgia and identify neurovascular contact. Trigeminal reflex testing is strongly recommended by EAN/EFIC/IASP for diagnosing secondary trigeminal neuralgia.^[2][5]
• First-line drug: carbamazepine. NICE CG173 offers carbamazepine as the initial treatment for trigeminal neuralgia. In the practical dosing consensus, carbamazepine is started at 200 mg, titrated 200 mg every 3 days, to a usual range of 200–1,200 mg daily in 2–4 doses, then tapered 200 mg every 7 days once remission occurs. Oxcarbazepine is an alternative first-line agent with a dose range of 300–1,800 mg in four doses, with fewer interactions.^[1][5]
• Second-line or add-on agents when carbamazepine fails or is not tolerated: lamotrigine, gabapentin, pregabalin, baclofen or (as specialist treatment) botulinum toxin type A. Other reported options include phenytoin, topiramate and tizanidine.^[5]
• Acute severe exacerbation (inability to eat or drink, severe loss of function): admit; opioids are generally ineffective and should be avoided. Intravenous fosphenytoin 15 mg/kg over 30 minutes or lidocaine 5 mg/kg over 60 minutes under cardiac monitoring can be highly effective, and topical lidocaine or local anaesthetic injections into trigger zones give transient relief.^[5]
• Refer for surgical opinion (microvascular decompression as first-line surgery for classical trigeminal neuralgia with neurovascular contact; ablative procedures or stereotactic radiosurgery when there is no contact or the patient is unfit) when drug treatment is insufficient or poorly tolerated.^[5]

Carbamazepine and oxcarbazepine are sodium-channel blockers and offer meaningful initial relief in about 90% of patients, although control may not be sustained long term. They must be used with the MHRA safety advice on anti-epileptic drugs in pregnancy. Oxcarbazepine is preferred when cardiac conduction or interactions are a concern.^[1][5]

Postherpetic neuralgia is pain persisting for at least 3 months after the onset or healing of herpes zoster, most often in the ophthalmic (V1) division of the trigeminal nerve or in thoracic dermatomes.^[4][6] As many as 20% of patients with herpes zoster develop it, and about half of cases occur in people over 60.^[6]

Acute shingles phase (aiming to limit viral replication and reduce the risk of chronic pain):

• Antivirals — acyclovir, famciclovir or valacyclovir — should be given within 72 hours of rash onset, and may still help while new lesions are forming.^[6]
• Analgesia for acute pain (short-acting opioid with paracetamol or an NSAID; gabapentinoids then a tricyclic for more severe pain), and consideration of early gabapentin plus valacyclovir to reduce PHN incidence.^[6]
• Corticosteroids are not routinely recommended for preventing PHN, though sometimes used in practice.^[6]
• Vaccination against varicella zoster (shingles) reduces the burden of illness and the incidence of PHN; protection may wane over time.^[6]

Chronic postherpetic neuralgia phase (the neuropathic pain first-line group applies, with a topical-first option on the trunk):^[6]

• First-line oral agents: gabapentin and pregabalin are the only systemic agents with FDA approval specifically for PHN. Tricyclic antidepressants (amitriptyline, nortriptyline, desipramine) are commonly effective but have anticholinergic and cardiac toxicities.
• Lidocaine 5% patch is a first-line topical therapy for PHN, most practical on the trunk: up to three patches per day. It has a favourable safety profile but is less practical for the head and face.^[6]
• Capsaicin 8% patch is a second-line therapy: up to four patches applied for one hour every 3 months or longer, after topical anaesthesia, by trained staff. Capsaicin 0.075% cream 3–5 times per day is another second- or third-line option.^[6]
• Opioids and tramadol are secondary or tertiary options when first-line treatment fails.
• Gabapentinoids are renally excreted, so dose according to creatinine clearance; immediate-release gabapentin at four times daily dosing is the common low-cost choice but many patients never reach the optimal dose of 1,800 mg/day because of titration difficulties.^[6]

All neuropathic pain benefits from explaining the condition, setting realistic expectations (drugs aim to reduce pain and improve participation, not to cure), sleep hygiene, pacing of activity, psychological and physical therapies via rehabilitation services, and treatment of depression and anxiety. Surgery and procedural interventions (nerve blocks, spinal cord stimulation) are specialist options.^[1][4]

Spasticity is treated in layers, from the general to the focal. Oral agents have a systemic but often sedating effect; botulinum toxin gives focal, reversible weakness; physical management is the foundation of all of it.^[7]

General (widespread or segmental) spasticity — oral or intrathecal agents:

• Baclofen — a GABA_B agonist that inhibits spinal reflexes. It is the most widely used oral antispasmodic. Dose: start 5 mg one to three times daily, increasing by 5 mg every 3 days, with an effective target around symptomatic relief; maximum 80 mg/day in one narrative review, while higher maintenance limits (if used) follow your local formulary. Taper rather than stop abruptly; withdrawal can cause anxiety, confusion, psychosis, seizures and rebound hypertonia. Reduce doses in renal impairment. Intrathecal baclofen, delivered by implanted pump, is the most effective option for refractory, widespread or severe spasticity of spinal or cerebral origin.^[7][8]
• Tizanidine — an alpha-2 agonist. Prescribing information: start 2 mg by mouth every 6 to 8 hours, as needed, up to 3 doses in 24 hours; increase by 2 to 4 mg per dose every 1 to 4 days; maximum total daily dose 36 mg; single doses above 16 mg have not been studied. Monitor liver enzymes at baseline and 1 month after reaching the maximum dose; avoid in severe renal or hepatic impairment without dose adjustment, and with strong CYP1A2 inhibitors. Discontinue gradually (reduce by 2–4 mg per day) to avoid rebound hypertension, tachycardia and hypertonia. Sedation, dry mouth, asthenia and dizziness are the commonest adverse effects.^[9]
• Other oral agents include dantrolene (direct muscle action, hepatotoxicity risk, requires liver-function monitoring), diazepam (especially for painful spasms, night-time use), and, off label, gabapentin.^[7]
• Intrathecal baclofen: screening with a 50 microgram bolus, then 75 microgram then (maximum) 100 microgram, monitoring response; maintenance by continuous infusion with slow titration (10–30% per day for spinal-origin, 5–15% per day for cerebral-origin spasticity). Withdrawal can be life-threatening and needs ICU care.^[8]

Focal spasticity — botulinum toxin type A (BoNT-A):

Botulinum toxin is a safe and effective treatment for focal and multifocal upper- and lower-limb spasticity, with level 1 evidence, and it is usually better tolerated than oral drugs for focal problems.^[7] It is given intramuscularly into selected muscles as part of a coordinated multidisciplinary programme with physical therapy before and after injection; it should never be used in isolation.^[7]

• Selection: focal or multifocal problems with a dynamic (spastic) component, clearly identified goals, and an assessment of possible negative impact on function (some patients rely on their spasticity for transfers or standing).^[7]
• Products have different schedules and are not interchangeable. Do not convert between units.
• Maximum recommended doses per adult injection session from the European consensus: Dysport (abobotulinumtoxinA) 1,500 MU (arm and leg), Botox (onabotulinumtoxinA) 200–240 units (arm) or 300 units (leg), Xeomin (incobotulinumtoxinA) 500 units (arm); per injection site 125 MU Dysport or 50 U Botox. Higher doses are reported in non-naive patients but carry increasing risk of systemic adverse effects.^[7]
• Onset and duration: the effect is temporary and wears off over weeks to a few months; repeat injections are scheduled by response rather than on a fixed calendar.^[7]
• Technique: target the motor end-plate where known; use EMG, electrical stimulation or ultrasound to localise deep or small muscles; start at effective but conservative doses and titrate.
• Adverse effects: local weakness from diffusion (transient), dysphagia when high doses are used around the neck or proximal arm (especially in patients with impaired swallowing), and rare generalised weakness. Warn patients to seek urgent care for breathing, swallowing or speech difficulty.
• Failure to respond should prompt review of injection accuracy, dose, muscle selection, fixed contracture, and (rarely) neutralising antibodies.^[7]

Multi-modal practice. A mixed pattern (focal plus widespread spasticity) is common, and interventions are combined — for example BoNT-A to target a single functional problem while baclofen manages a background of more generalised tone. Physical management — positioning, stretch, splinting, casting, exercise and postural care — runs throughout. Phenol nerve blocks, serial casting, orthopaedic surgery and (in selected severe cases) selective dorsal rhizotomy are specialist adjuncts.^[7]

• Neuropathic pain: early review after starting or changing treatment (titration, tolerability, adverse effects), then regular reviews covering pain, function, sleep, mood, adverse effects and continued need.^[1]
• Trigeminal neuralgia: arrange early follow-up to assess dose titration progress and tolerability; reduce the dose to the lowest maintenance level or stop after remission.^[5]
• Spasticity: define goals and outcome measures, reassess regularly and before each repeat injection, and review whether the drug still works before each course.^[7][8]

• Neuropathic pain: severe pain; pain limiting daily life, sleep or participation; deterioration of the underlying condition; failure of two or three first-line drugs; trigeminal neuralgia not responding to carbamazepine. Refer to a specialist pain service or condition-specific service; there is no need to wait until everything has been tried.^[1]
• Spasticity: any patient with disabling focal spasticity who may benefit from BoNT-A, and any patient with severe or refractory widespread spasticity who may benefit from intrathecal baclofen; refer to multidisciplinary spasticity or rehabilitation services.^[7]

• Of the pain: chronic sleep disturbance, depression, anxiety, deconditioning, loss of work, fatigue, and medication side effects. Systemic drugs (opioids, benzodiazepines, polypharmacy) can produce falls, cognitive impairment and dependence, particularly in older adults.
• Of the diseases: progression of diabetic, toxic or inflammatory neuropathy; autonomic complications; skin breakdown and pressure injury in sensory loss.
• Of treatment: opioid dependence and opioid-induced hyperalgesia from long-term opioid use; TCA cardiotoxicity; gabapentinoid misuse; baclofen withdrawal and toxicity; botulinum toxin dysphagia, transient excessive weakness and (rarely) systemic spread.
• Of spasticity: pain, contracture, joint deformity, pressure ulcers, impaired sitting, hygiene and sleep, autonomic dysfunction, reduced quality of life and carer burden.^[7]

Neuropathic pain is usually chronic, and first-line drugs provide less than satisfactory relief in many patients.^[4] Set expectations accordingly: the aim is meaningful reduction in pain and improved participation, usually requiring stepwise drug trials, dose optimisation and non-drug measures over months. Some conditions have a better course: many patients with trigeminal neuralgia have remitting paroxysmal pain; postherpetic neuralgia often eases over months to years; spasticity after stroke may plateau or improve with rehabilitation. After a single drug failure, switching to another first-line agent is the correct next step, and combination approaches help refractory pain.^[1][6]

There is no screening or primary prevention for most neuropathic pain. Secondary prevention targets the underlying condition:

• Diabetes: glycaemic control, foot inspection, protective footwear and early treatment of neuropathy.
• Herpes zoster: antiviral treatment within 72 hours of rash and, where available, shingles vaccination.^[6]
• Trauma: early, adequate analgesia and management of nerve injuries and wounds.
• Cancer: careful assessment of nerve compression or infiltration, with early neuropathic pain management.

For spasticity, early positioning, stretch and rehabilitation after acquired brain injury help prevent fixed contracture; early assessment in a specialist clinic is preferable to waiting for complications.^[7]

• Older adults. Postherpetic neuralgia is mainly a disease of older people, and the same group is least tolerant of tricyclic and opioid side effects. Gabapentinoids, lidocaine patches, low doses and slow titration are often preferred. The American Geriatrics Society Beers criteria advise avoiding TCA use in older adults because of anticholinergic and cognitive effects.^[6]
• Renal impairment. Gabapentin, pregabalin and tizanidine are cleared renally; reduce doses and monitor. Baclofen also needs dose reduction or avoidance in severe renal impairment.^[6][8][9]
• Pregnancy and breastfeeding. MHRA safety advice on anti-epileptic drugs in pregnancy applies to carbamazepine, valproate and topiramate. Baclofen is pregnancy category C with reported neonatal withdrawal after intrauterine exposure. Gabapentinoid pregnancy guidance must be followed. Get specialist advice; the safest option is to manage with the least teratogenic effective combination.^[1][8][9]
• Children. Neuropathic pain in children is managed by specialist services. Tizanidine has not established safety in children. Spasticity in children (for example cerebral palsy) uses a different evidence base; botulinum toxin, oral baclofen and intrathecal baclofen are all used, with attention to growth, swallowing and surgery.^[7][9]
• Immunocompromised patients. HIV, cancer and post-transplantation neuropathy require treatment of the underlying condition plus standard neuropathic pain drugs, with vigilance for drug interactions and infection.

• Diagnosis is clinical. In the absence of QST, skin biopsy or advanced imaging, a probable grade of neuropathic pain is sufficient to start treatment, and the IASP grading system was designed with this in mind.^[3]
• Use the cheapest effective oral drugs: amitriptyline is inexpensive and effective for many neuropathic pains; generic gabapentin is the usual low-cost choice for post-herpetic neuralgia, even though optimal doses are often not reached.
• Lidocaine patch is effective but expensive; if unavailable, lidocaine gel or basic emollients with cool compresses can be tried. Capsaicin cream 0.075% is cheap but the burning limits tolerance.
• Trigeminal neuralgia: carbamazepine is low-cost and dramatically effective; if MRI is unavailable, use clinical diagnosis and ensure access to neurosurgical referral.
• Spasticity: teach positioning, stretch, seating and pressure-care before drugs; baclofen and diazepam are inexpensive; botulinum toxin is expensive and usually only available in specialist urban centres. When a patient cannot access BoNT-A, good physical management plus oral antispasmodics is the realistic plan.
• Refer early by the cheapest route (training, telemedicine) rather than waiting for complications such as contractures or pressure ulcers.

• Neuropathic pain is pain caused by a lesion or disease of the somatosensory nervous system, graded possible, probable or definite.
• It is common (up to 10% of the population) and usually chronic, and first-line drugs help many but not all patients.
• Typical sensory features are burning, shooting, electric shock-like pain with allodynia, and negative sensory signs in a neuroanatomically plausible distribution.
• NICE CG173 first-line drugs (except trigeminal neuralgia) are amitriptyline, duloxetine, gabapentin and pregabalin; if one fails, switch to one of the others; acute rescue tramadol only. ^[1]
• NICE also lists drugs that should not be started in non-specialist settings, including morphine, oxcarbazepine, topiramate, venlafaxine, valproate, lamotrigine and long-term tramadol.
• Capsaicin cream 0.075% is a topical alternative for localised pain; lidocaine 5% patch provides local analgesia with a favourable safety profile.
• Trigeminal neuralgia is treated first with carbamazepine (200–1,200 mg/day); oxcarbazepine is an alternative.
• Postherpetic neuralgia is treated with the same first-line group, with lidocaine patch and capsaicin (8% patch second line) as topical options; acute shingles is treated with antivirals within 72 hours.
• Spasticity is velocity-dependent muscle overactivity after central nervous system damage; pain related primarily to spasticity is classified as musculoskeletal pain.
• Generalised spasticity: baclofen (start 5 mg 1–3 times daily, maximum 80 mg/day in one review, 100 mg/day in UK practice) and tizanidine (start 2 mg every 6–8 hours, maximum 36 mg/day).
• Focal spasticity: botulinum toxin type A, injected by experienced clinicians with EMG or ultrasound guidance, at least 3 months between courses, never in isolation from physical therapy.
• Pain primarily from spasticity improves when tone is reduced; treat pain, tone and posture together.