Pain in neurology Jiří Klempíř Petr Dočekal Neurologická klinika 1. LF UK a VFN Praha
Definition, general principles of diagnostics and therapy of pain
Pain is unpleasant sensory and emotional experience associated with actual or potential tissue damage, or is described in terms of such damage. Perception of pain is individual matter. Identical stimulus may lead to different pain perception in different individuals or in the same individual under various circumstances.
Classification of pain according to generation mechanism Nociceptive somatic p. caused by irritation.of nerve endings by mechanical, thermic, chemical stimuli; responds to analgesic therapy. Nociceptive visceral p. - dull, pressure, sharp, jerked, locatable; responds to analgesics. Neuropathic p. constant, burning, stinging, paroxysmal stabbing, shooting. Responds better to coanalgesics than to analgesics. Psychogenic p. Dysautonomic p. complex regional pain syndrome, causalgia Mixed p.
Character Purpose Mechanism Autonomic r. Mental r. Behavior Pharmacotherapy Analgesic effect Treatment strategy Duration Acute p. Symptom Defense of organism Simple Sympathetic +++ Anxiety Defensive, reactive Analgesics Marked step down < 3 monthes Chronic p. Syndrome Destructive Complex Sympathetic s. + Depression Learned, painful Analgesics, adjuvant th. Often low step up > 3 months
Medical history in case of pain Onset of the first signs of pain Character, several types of pain Localization Intensity Duration Provoking and relieving factors Somatic symptoms Cognitive and behavioral disturbances Past and present treatment and its effects
Non-opioid analgesics Paracetamol, metamizole Non-steroidal anti-inflamatory medications (NSAIDs) Opioids Weak opioids codein, dihydrocodein, tramadol Strong opioids morphine, petidine, phentanyl, piritramide, buprenorphine, oxycodone, hydromorphone, methadone Weak opioids identical or lower efficacy than NSA.
Adjuvat analgesics - anticonvulsants Gabapentin sodium and calcium channels, low affinity to GABA receptors, enhanced release of GABA Pregabalin voltage-gated calcium channels, low GABAergic effect Carbamazepine blockage of voltage-gated sodium channels, blockage of L-calcium channels, enhanced release of serotonin, inhibition of glutamate NMDA and adenosine A1 receptors
Adjuvat analgesics - antidepressants Mechanism of effect serotonin and noradrenaline reuptake inhibitors Amitriptyline, imipramine, dosulepin Venlafaxine, milnacipram, duloxetine
Visual analog scale of pain (VAS) no pain pain as bad as it could possibly be
Assessment of analgesic effect Evaluation by a patient, his family, caregivers, physician Has been at least partial control of pain achieved? (Subj. well tolerable pain - VAS lower than 4. If weak opioids don t bring relief until 72 hours strong opioids indicated.) Is there deterioration of functional capability of a patient? Is favorable ratio benefit/side effects achieved? What is overall quality of patient s life? (mental condition, sleep, reengaging in previous activities, improvement of performance)
Pain of head and neck
Painful structures of head and neck Mechanical and inflammatory damage to extra- and intracranial arteries Mechanical and inflammatory damage to large intracranial veins and to their shields Mechanical or inflammatory damage to cranial and cervical spinal cord nerves Mechanical or inflammatory damage to skull, teeth and cervical pain Spasm, inflammation or trauma of head and neck muscles Irritation of menings a intracranial hypertension
Primary headache» migraine» tension headache» cluster headache Secondary headache» trauma, infection, vascular etiology, intoxication, metabolic, neuralgia, intracranial expansion,.
Epidemiology of migraine 12% of population 3x more common in women Most frequently between 12-40 years of age Familial incidence Single paroxysm of migraine in an individual who doesn t suffer from migraine otherwise - not rare
Pathogenesis of migraine
Migraine Migraine without aura - simple (80%) Migraine with aura - classical (18%) Stages of migraine:» prodromal stage» aura» migrainous headache» postdromal phase
Prodromal stage Present in approximately one half of patients before development of migrainous headache Lasts for several hours or days Mood disorders in both positive and negative sense, sleep disturbances, enhanced appetite and motor agitation
Aura Focal symptoms arising from cortex or brainstem Praha & EU: Investujeme do vaší budoucnosti Lasts for minutes, maximal duration 1 hour Visual aura blurred vision, phosphenes, colourful flashes, hemianopsia, scotomas, deformations of objects, geometric figures Sensory aura paresthesia in different body parts Rarely dysarthria, phatic dysfunctions and central paresis Aura symptoms may combine together but their spectrum doesn t transform much throughout the lifetime.
Migrainous headache Follows aura immediately, no later than within 60 minutes but they can occur at the same time. Most intensive in frontotemporal area, pulsating character, unilateral and bilateral as well. Status migraenosus - duration longer than 72 hours Osmophobia, odorophobia, vegetative dysfunction (disruptions of thermoregulation, hyperhidrosis, diarrhoea), deficit of concentration, signs of anxiety and depression Physical activity leads to worsening of pain
Postdromal stage After offset of pain May last for several days Fatigue, exhaustion, irritability, euphoria, changes of appetite
Dg. criteria of migraine without aura A. At least 5 attacks must fulfill criteria B-D B. Duration of headache without medication - 4-72 hours C. Pain may be characterized at least by 2 of following features Unilateral localization Pulsating character Moderate to severe intensity Deterioration after physical effort D. Pain is accompanied by at least 1 of these symptoms: Nausea or vomiting Photofobia or phonophobia
Hemiplegic m. Other variants of migraine Basilar m. - aura arising from irritation of brainstem or occipital cortex. At least 2 of these symptoms: temporal and nasal hemianopsia, dysarthria, vertigo, tinnitus, hypacusis, diplopia, ataxia, bilateral paresthesias, parapareses and consciousness disturbances. Ophthalmoplegic m. oculomotor disruption, most frequently in oculomotor nerve homolaterally to affected hemicranium. Retinal m. monocular scotomas or monocular blindness lasting longer than one hour, followed by development of migrainous headache. Exclude thromboembolic etiology!
Praha & EU: Investujeme do vaší Acute budoucnosti treatment of migraine Nonsteroid analgesics acetylsalicylic a., ibuprofen, paracetamol, metamizole, diclofenac Triptans - selective agonists of 5-HT1D and 5-HT1B receptors - sumatriptan, eletriptan, frovatriptan, zolmitriptan, naratriptan, Antiemetics - metoclopramide, thietylperazine Sedative medication - benzodiazepines Combined medications with caffeine, antiemetic
Prophylactic treatment of migraine Efficient prophylaxis decreases number of paroxysms by 50% within 3 months Anticonvulsants valproic a., topiramate Antidepressants - amitriptyline, SSRI, SNRI. Beta blockers - propranolol, metoprolol Ca channel blockers - flunarizine, cinnarizine Lifestyle changes!!!
Tension headache A. A patient has to fulfill criteria at least in 2 points: B. Pain of pressure or constricting character C. Bilateral localization of pain D. Pain of mild to moderate intensity E. Pain doesn t get worse after physical activity, is accompanied by neither nausea nor vomiting, but slight photophobia or phonophobia may be present
Tension headache (TH) The most common of all headaches Etiology not clear, often in people with symptoms of anxiety, depression, with long-term stress. Sometimes with increased tension of pericranial muscles Chronic TH more than 15 days in 1 month Differential diagnosis milder migraine, cervicocranial syndrome Therapy nonsteroid analgesics for transient relief - antidepressants - lifestyle changes, relaxation, aerobic sports psychotherapy
Dg. criteria for Cluster headache I. A. At least 5 attacks meeting criteria B-D B. Intensive unilateral orbital, supraorbital and/or temporal pains lasting for 15-180 min C. At least one of the following symptoms on the side of pain: Hyperemia of conjunctiva Lacrimation Rhinorrhea Hyperhidrosis of forehead or face Miosis Ptosis Palpebral oedema Nasal congestion
Dg. Criteria for Cluster headache II. D. Attack frequency: 1-8x per day E. Medical history, neurological examination and auxiliary examination methods don t indicate secondary headache; or secondary headache may be present but onset of cluster headache is not associated with this secondary disease
Cluster headache Prevalence much lower than in migraine (1:6-50), more common in men Altered vasomotor functions of ophthalmic artery, activation of hypothalamus, of sympathetic system and of trigeminovascular complex Alcohol, vasodilating substances (histamine, nitrates), solvents and perfumes Often circadian periodicity, not depending on provoking factors Therapy - normotensive inhalation of pure oxygen 7-10 liters /min or injection of sumatriptan
Chronic daily headache Longer than 15 days in 1 month and single attacks last longer than 4 hours 60 % of migraine, 30 % of episodic tension headache transform into chronic and later to daily headache Risk factors: abuse of analgesics (particularly of those combined with codein), personality disorders (tendencies towards depression, anxiety), external stressing factors (related to family, work, etc.) and menopause. It is necessary to exclude secondary cause!
Headache warning signs I. Sudden onset, intensiveness of headache, during Praha & EU: Investujeme do vaší budoucnosti physical activity or change of body position Headache occurs for the first time in a patient over 40 years of age Increasing frequency and intesity of headache Novel type or change of headache character Continually developing atypical headache non-responsive to common therapy Headache that is always in the same location
Headache after trauma Headache warning signs II. Headache in a patient with tumor or HIV infection H. that deteriorates with increase in intracranial pressure Headache associated with seizures Focal neurological symptoms Cognitive deficit Quantitative or qualitative disturbance of consciousness
Cervicocranial syndrome Pain localized in nuchal and occipital area, with possible projection into frontal, orbital and parietal areas or towards vertex and ears. Pains are preceded by movements of cervical spine or by certain position; or they are accentuated by these factors. Conidition meets at least one of the following criteria: Limited passive mobility of cervical spine Altered tone, shape and overall consistence of paravertebral muscles after active and passive movements Abnormal sensitivity of nuchal muscles.
Subarachnoidal hemorrhage Rupture of an aneurysm or extension of intraparenchymal hemorrhage Cruel pain develops immediately after onset of bleeding; is localized inside the head, often unilaterally, but often generalizes. Meningeal syndrome Focal symptoms Sentinel pain microskopic bleedings, up to 50% Atypical course not rare
Dissecting carotid artery unilateral burning, pulsating headache in frontal, periorbital and neck areas, Horner s syndrome, pareses of cranial nerves, hemispheric symptoms Dissecting vertebral artery intensive pain in occipital area and cervicocranial border. Symptoms may fluctuate depending on position of head and can develop into the condition of ischemia of lateral parts of medulla and cerebellum within several days. Thromboses of venous sinuses Arterial hypertension > 200/120 mmhg
Adverse effects of medications - indomethacin, cimetidine, ranitidine, statins, fibrates, ciclosporin, antidepressants, opioid and nonopioid analgesics, ergotamine and triptans, nitrates, phosphodiesterase inhibitors Addictive substances ethanol, organic solvents, psychotropic drugs Neuroinfections Inflammation of paranasal sinuses Whiplash injury consequence of acceleration and deceleration trauma of cervical spine Sleep apnea syndrome
Glaucoma attack closed angle in the anterior chamber of eyeball severe pain in the depth of bulbus projecting into forehead in the area of the 1st branch of n.v, with vision disturbances, nausea, vomiting and marked vegetative symptoms Provoked by mydriatic substances, dimness, stress, atropine, but even by strong miotic agents First aid - glycerol, acetazolamide, timolole a pilocarpine. Retrobulbar neuritis Pain behind the eye may precede vision disturbances by several hours or days.
Neurological examination Normal finding Meningeal syndrome Focal findings CT of brain CT of brain CT,MR, MRAg of brain, US Normal finding Lumbar puncture tumor, hydrocephalus, hematoma, AV malformation, dissecting a., venous thrombosis Inflammation Normal finding SAH Purulent Serous Neurosurgery Primary headache
Neuropathic pain
Neuropathic pain Peripheral:» neuralgia of cranial nerves» polyneuropathy» trauma of peripheral nerve Central:» thalamic pain» phantom pain» pain in condition with CNS lesion
Praha & EU: Investujeme do vaší Primary budoucnosti trigeminal neuralgia Prevalence 7:10000 In 80% of cases demyelinating lesions in the portion of the nerve that enters the pons, in contact with vascular structures (superior cerebellar artery and its branches, anterior cerebellar artery, veins in the area of petrose bone) indications for decompression
Dg. Criteria of primary trigeminal neuralgia A. Paroxysmal pain attacks in the face that last for several seconds and less than 2 minutes B. Pain presents with at least 4 of the following characteristics: Localization in some of trigeminal branches Sudden, intensive, sharp, superficial, stabbing, burning pain High intensity of pain Pain can be triggered from trigger zones or by certain activities, such as brushing teeth, chewing A patient is asymptomatic during intervals betweens paroxysms C. Normal neurological finding D. Attacks repeat in a stereotypic manner in individual patients E. Other possible causes of pain in the face have been excluded by all available methods
Praha & EU: Investujeme do vaší Secondary budoucnosti trigeminal neuralgia May be clinically similar to primary neuralgia Trigger zone may be absent, attacks can be longer or persist. Sensory disturbance or other focal symptoms may be present. Most frequently odontogenic etiology Postherpetic neuralgia affects particularly the 1st branch of n.v and only rarely the 2nd branch or otic ganglion
Distal symetric polyneuropathy Motor symptoms reduced or extinct tendon reflexes, muscle weakness, muscle atrophy, gait and standing disorders, ataxia, falls Sensory symptoms pain, paresthesia (tingling, pins and needles sensation, burning etc.), hypesthesia, anesthesia, cramps Autonomic symptoms - Screening lab. tests - blood glucose, serum B12, serum protein immunofixation electrophoresis Electromyography, nerve and muscle biopsy, genetic testing Common etilogy - diabetes, alcohol abuse, intoxication, paraneoplastic, chemotherapy, Guillain-Barré syndrome, Lyme borreliosis
Treatment of neuropathic pain 1. Treatment of primary cause 2. Coanalgesics in monotherapy - anticonvulsants tricyclic antidepressants (TCA) serotonin and noradrenaline reuptake inhibitors (SNRI) 3. Combination of coanalgesics: anticonvulsants with TCA or SNRI 4. Combination of medication from point 2 or 3 with opioids Non-pharmacological intervention is an integral part of all 4 points. Algorithm adapted according to:efns guidelines on pharmacological treatment of neuropathic pain. Attal N et al. European Journal of Neurology 2006;13:1153 1169