Pain



Pain





Headache


I. General Considerations



  • Occurs when peripheral nocioceptors are stimulated in response to tissue injury, visceral distension, or when peripheral or central pain pathways are damaged or activated inappropriately


  • Cranial pain sensitive structures include the scalp, middle meningeal artery, dural sinuses, falx cerebrii, proximal segments of large pial arteries.


  • Sensory stimuli from the cranium are conveyed centrally via the trigeminal nerves for structures above the tentorium and the anterior and middle cranial fossae, and via C1 through C3 for structures in the posterior fossa and inferior surface of the tentorium.


  • Posterior fossa lesions usually produce occipitonuchal pain, and supratentorial lesions produce frontotemporal pain.


II. Headache Classification (Derived from the International Classification of Headache Disorders, 2nd Edition)



  • The Primary Headaches



    • Migraine



      • Migraine without aura


      • Migraine with aura



        • Typical aura with migraine headache


        • Typical aura with nonmigraine headache


        • Typical aura without headache


        • Familial hemiplegic migraine


        • Sporadic hemiplegic migraine


        • Basilar-type migraine


      • Childhood periodic syndromes that are commonly precursors of migraine



        • Cyclic vomiting


        • Abdominal migraine


        • Benign paroxysmal vertigo of childhood


      • Retinal migraine


      • Complications of migraine



        • Chronic migraine


        • Status migrainous


        • Persistent aura without infarction


        • Migrainous infarction


        • Migraine-triggered seizure



      • Probable migraine



        • Probable migraine without aura


        • Probable migraine with aura


        • Probable chronic migraine


    • Tension-type headache



      • Infrequent episodic tension-type headache—associated or not associated with pericranial tenderness


      • Frequent episodic tension-type headache—associated or not associated with pericranial tenderness


      • Chronic tension-type headache—associated or not associated with pericranial tenderness


      • Probable tension-type headache



        • Probable infrequent episodic tension-type headache


        • Probable frequent episodic tension-type headache


        • Probable chronic tension-type headache


    • Cluster headache and other trigeminal autonomic cephalgias



      • Cluster headache



        • Episodic cluster headache


        • Chronic cluster headache


      • Paroxysmal hemicrania



        • Episodic paroxysmal hemicrania


        • Chronic paroxysmal hemicrania


      • Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT).


      • Probable trigeminal autonomic cephalgia



        • Probable cluster headache


        • Probable paroxysmal hemicrania


        • Probable SUNCT


    • Other primary headaches



      • Primary stabbing headache


      • Primary cough headache


      • Primary exertional headache


      • Primary headache associated with sexual activity



        • Preorgasmic headache


        • Orgasmic headache


      • Hypnic headache


      • Primary thunderclap headache


      • Hemicrania continua


      • New daily persistent headache


  • The Secondary Headaches



    • Headache attributed to head and/or neck trauma



      • Acute posttraumatic headache



        • Acute posttraumatic headache attributed to moderate or severe head injury


        • Acute posttraumatic headache attributed to mild head injury


      • Chronic posttraumatic headache



        • Chronic posttraumatic headache attributed to moderate or severe head injury


        • Chronic posttraumatic headache attributed to mild head injury



      • Acute headache attributed to whiplash injury


      • Chronic headache attributed to whiplash injury


      • Headache attributed to traumatic intracranial hematoma—epidural or subdural hematoma


      • Headache attributed to other head and/or neck trauma—acute and chronic types


      • Postcraniotomy headache—acute and chronic types


    • Headache attributed to cranial or cervical vascular disorders



      • Headache attributed to ischemic stroke or transient ischemic attack


      • Headache attributed to nontraumatic intracranial hemorrhage—intracerebral or subarachnoid


      • Headache attributed to unruptured vascular malformation



        • Headache attributed to saccular aneurism


        • Headache attributed to arteriovenous malformation


        • Headache attributed to dural arteriovenous fistula


        • Headache attributed to cavernous angioma


        • Headache attributed to encephalotrigeminal or leptomeningeal angiomatosis (Sturge-Weber syndrome)


      • Headache attributed to arteritis



        • Headache attributed to giant cell arteritis


        • Headache attributed to primary central nervous system angiitis


        • Headache attributed to secondary central nervous system angiitis


      • Carotid or vertebral artery pain



        • Headache or facial or neck pain attributed to arterial dissection


        • Postendarterectomy headache


        • Carotid angioplasty headache


        • Headache attributed to intracranial endovascular procedures


        • Angiography headache


      • Headache attributed to cerebral venous thrombosis


      • Headache attributed to other intracranial vascular disorder



        • Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy


        • Mitochondrial encephalopathy, lactic acidosis, and strokelike episodes


    • Headache attributed to nonvascular intracranial disorder



      • Headache attributed to high cerebrospinal fluid (CSF) pressure



        • Headache attributed to idiopathic intracranial hypertension


        • Headache attributed to intracranial hypertension secondary to metabolic, toxic, or hormonal causes


        • Headache attributed to intracranial hypertension secondary to hydrocephalus


      • Headache attributed to low CSF pressure



        • Postdural puncture headache


        • CSF fistula headache


        • Headache attributed to spontaneous (or idiopathic) low CSF pressure


      • Headache attributed to noninfectious inflammatory disease



        • Headache attributed to neurosarcoidosis


        • Headache attributed to aseptic (noninfectious) menigitis


        • Headache attributed to other noninfectious inflammatory disease


        • Headache attributed to lymphocytic hypophysitis



      • Headache attributed to intracranial neoplasm



        • Headache attributed to increased intracranial pressure or hydrocephalus caused by neoplasm


        • Headache attributed directly to neoplasm


        • Headache attributed to carcinomatous meningitis


        • Headache attributed to hypothalamic or pituitary hypersecretion or hyposecretion


      • Headache attributed to intrathecal injection


      • Headache attributed to epileptic seizure



        • Hemicrania epileptica


        • Postseizure headache


      • Headache attributed to Chiari malformation type 1


      • Syndrome of transient headache and neurologic deficits with CSF lymphocytosis


      • Headache attributed to other nonvascular intracranial disorder


    • Headache attributed to a substance or its withdrawal



      • Headache induced by acute substance use or exposure



        • Nitrous oxide donor-induced headache—immediate and delayed types


        • Phosphodiesterase inhibitor-induced headache


        • Carbon monoxide-induced headache


        • Alcohol-induced headache—immediate and delayed types


        • Headache induced by food components and additives—monosodium glutamateinduced headache


        • Cocaine-induced headache


        • Cannabis-induced headache


        • Histamine-induced headache—immediate and delayed


        • Calcitonin gene-related peptide-induced headache—immediate and delayed types


        • Headache as an acute adverse event attributed to medication used for other indications


        • Headache induced by other acute substance use or exposure


      • Medication overuse headache



        • Ergotomine-overuse headache


        • Triptan-overuse headache


        • Analgesic-overuse headache


        • Opioid-overuse headache


        • Combination medicine-overuse headache


        • Headache attributed to other medication overuse


        • Probable medication-overuse headache


      • Headache as an adverse event attributed to chronic medication—exogenous hormone-induced headache


      • Headache attributed to substance withdrawal


    • Headache attributed to infection



      • Headache attributed to intracranial infection



        • Headache attributed to bacterial meningitis


        • Headache attributed to lymphocytic meningitis


        • Headache attributed to encephalitis


        • Headache attributed to brain abscess


        • Headache attributed to subdural empyema



      • Headache attributed to systemic infection



        • Headache attributed to systemic bacterial infection


        • Headache attributed to systemic viral infection


        • Headache attributed to other systemic infection


      • Headache attributed to HIV/AIDS


      • Chronic postinfectious headache



        • Chronic postbacterial meningitis headache


    • Headache attributed to disorder of homeostasis



      • Headache attributed to hypoxia and/or hypercapnia



        • High-altitude headache


        • Diving headache


        • Sleep apnea headache


      • Dialysis headache


      • Headache attributed to arterial hypertension



        • Headache attributed to pheochromocytoma


        • Headache attributed to hypertensive crisis without hypertensive encephalopathy


        • Headache attributed to hypertensive encephalopathy


        • Headache attributed to preeclampsia


        • Headache attributed to eclampsia


        • Headache attributed to acute pressor response to an exogenous agent


      • Headache attributed to hypothyroidism


      • Headache attributed to fasting


      • Cardiac cephalgia


      • Headache attributed to other disorder of homeostasis


    • Headache or facial pain attributed to disorder of cranium, neck, eyes, ears, nose, sinuses, teeth, mouth, or other facial or cranial structures



      • Headache attributed to disorder of cranial bone


      • Headache attributed to disorder of neck



        • Cervicogenic headache


        • Headache attributed to retropharyngeal tendonitis


        • Headache attributed to craniocervical dystonia


      • Headache attributed to disorder of eyes



        • Headache attributed to acute glaucoma


        • Headache attributed to refractive errors


        • Headache attributed to heterophoria or heterotropia (latent or manifest squint)


        • Headache attributed to ocular inflammatory disorder


      • Headache attributed to disorder of ears


      • Headache attributed to rhinosinusitis


      • Headache attributed to disorder of teeth, jaws, or related structures


      • Headache or facial pain attributed to temperomandibular joint disorder


      • Headache attributed to other disorder of cranium, neck, eyes, ears, nose, sinuses, teeth, mouth, or other facial or cervical structures


    • Headache attributed to psychiatric disorder



      • Headache attributed to somatisation disorder


      • Headache attributed to psychotic disorder



  • Cranial neuralgias, central and primary facial pain and other headaches



    • Cranial neuralgias and central causes of facial pain



      • Trigeminal neuralgia—classic and symptomatic types


      • Glossopharyngeal neuralgia—classic and symptomatic types


      • Nervus intermedius neuralgia


      • Superior laryngeal neuralgia


      • Nasociliary neuralgia


      • Supraorbital neuralgia


      • Other terminal branch neuralgias


      • Occipital neuralgia


      • Neck-tongue syndrome


      • External compression headache


      • Cold-stimulus headache



        • Headache attributed to external application of a cold stimulus


        • Headache attributed to ingestion or inhalation of a cold stimulus


      • Constant pain caused by compression, irritation or distortion of cranial nerves or upper cervical roots by structural lesions


      • Optic neuritis


      • Ocular diabetic neuropathy


      • Head or facial pain attributed to Herpes Zoster



        • Head or facial pain attributed to acute Herpes Zoster


        • Postherpetic neuralgia


      • Tolosa-Hunt syndrome


      • Ophthalmoplegic “migraine”


      • Central causes of facial pain



        • Anesthesia dolorosa


        • Central poststroke pain


        • Facial pain attributed to multiple sclerosis


        • Persistent idiopathic facial pain


        • Burning mouth syndrome


        • Other cranial neuralgia or other centrally mediated facial pain


    • Other headache, cranial neuralgia, central or primary facial pain



      • Headache not elsewhere classified


      • Headache unspecified


III. Migraine Headache



  • Definition and cause



    • A primary episodic headache disorder characterized by various combinations of neurologic, gastrointestinal, and autonomic changes


    • Approximately 15% of women, 6% of men, and 4% of children in the U.S. affected


    • Onset age, 5 to 11 in men; 12 to 17 in women


    • Gender ratio 3:1 women to men


    • Higher incidence in lower socioeconomic classes


    • Associated conditions



      • Stroke


      • Epilepsy


      • Affective disorders and anxiety



      • ? certain personality traits


      • Mitral valve prolapse, irritable bowel syndrome, fibromyalgia, benign positional vertigo, Raynauds, and so forth


    • Affects 28 million in U.S. with severe headache


    • Decreased productivity—$13 billion per year


    • Constitutes 4% of all physician office visits


  • Pathophysiology



    • Migraine genetics

















      Gene (Locus)

      Association


      tRNALeu (UUR) (mitochondrial)

      MELAS


      CACNL1A4 (chromosome 19p13)

      Codes for P/Q calcium channel (found in 50% of FHM cases)


      DRD2 (chromosome 11q23)

      Codes for G protein-coupled D2 dopamine receptor (found in some cases of migraine with aura)


      FHM, familial hemiplegic migraine; MELAS, mitochondrial encephalopathy, lactic acidosis, and strokelike episodes.




      • Familial hemiplegic migraine—chromosomes 1and 19-defect in P/Q-type Ca channel, inhibiting release of 5 HT


      • 75% or more of migraineurs report positive family history


    • Migraine is a biologically determined, episodic syndrome of heightened sensory sensitivity.


    • Migraineurs are more likely to have been prone to motion sickness as children.


    • There is a state of dopaminergic hypersensitivity and serotonergic hyposensitivity in migraine.


    • Stages of migraine



      • Prodrome—beginning 24 hours before headache; 25% of patients note elation, irritability, depression, hunger, thirst, or drowsiness


      • Aura



        • Spreading depression—reduction in cerebral blood flow moving from posterior to anterior at 2 to 3 mm/min (potassium-liberating, preceded by wave of increased metabolic activity)


        • Probably involves state of neuronal hyperexitability (involving glutamate, Mg, aspartate)


      • Headache phase



        • Central sensitization (“wind-up”)


        • Sterile neurogenic inflammation


        • Role of serotonin, calcitonin gene-related peptide, substance P, and the trigeminovascular system (trigeminocervical complex)


        • Modulation of pain transmission in the midline brainstem nuclei


      • Resolution phase


  • Clinical features



    • Aura



      • Focal neurologic symptoms preceding, accompanying, or rarely following the headache


      • Develops over 5 to 20 minutes and lasts <60 minutes



      • Usually visual; can be motor, sensory, or involve language or brainstem phenomena


      • Can occur without the headache-“acephalgic” migraine, late-life migraine equivalent


    • Headache phase



      • Unilateral throbbing pain of moderate to marked intensity, gradual onset, aggravated by physical activity, lasting 4 to 72 hours


      • Pain may be bilateral (40%)


      • Accompanied by anorexia, nausea and vomiting, sensory sensitivity (such as visual changes, nasal congestion, hunger, diarrhea, cramps, polyuria, pallor, sweating, hot and cold sensations, facial edema, scalp tenderness, dizziness)


    • Resolution phase



      • Pain wanes


      • Patient may feel tired, irritable, may have impaired concentration, scalp tenderness, mood changes, depression.


      • Neurologic symptoms may follow pain resolution-(“complicated” migraine, persistent aura without infarction, migrainous infarction).


    • Diagnostic criteria



      • Migraine without aura



        • At least five attacks


        • Lasts 4 to 72 hours


        • Has two of the following characteristics



          • Unilateral location


          • Pulsating quality


          • Moderate to severe intensity


          • Aggravation by routine physical activity


        • During headache at least one of the following



          • Nausea and/or vomiting


          • Photophobia or phonophobia


          • Not attributed to another disorder


      • Migraine with aura (classic migraine)



        • At least two attacks


        • At least three of the following



          • Fully reversible aura


          • At least one aura evolves gradually over at least 4 minutes or two or more symptoms evolve in succession


          • Each symptom lasts <60 minutes; if more than one aura evolves in succession, overall duration may be increased


          • Headache begins during or follows the aura with a symptom-free interval of <60 minutes


      • Basilar-type migraine



        • Migraine with an aura clinically localized to the brainstem


        • Two or more aura symptoms of the following types: dysarthria, vertigo, tinnitus, loss of hearing, diplopia, ataxia, decreased level of consciousness, simultaneous bilateral visual, motor or sensory disturbances


      • Confusional migraine



        • Typical aura and headache


        • Confusion may precede or follow the headache



      • Ophthalmoplegic migraine



        • No longer considered true migraine


        • Headache associated with ocular cranial nerve (CN) palsies—usually CN III, but can be CN IV, CN VI, and so forth


        • Probably represents an idiopathic inflammatory neuritis


      • Hemiplegic migraine



        • Both familial and sporadic forms


        • Usually begin earlier than typical migraine


        • Hemiplegia may last from minutes to weeks


        • Headache may be absent


        • Familial form autosomal dominant (chromosomes 1 and 19p13); P/Q-type calcium channel mutation


        • Can have fever, confusion, meningeal signs, coma, cerebellar ataxia, etc.


    • Magnetic resonance imaging (MRI)abnormalities in migraine patients



      • Particularly common in migraine with aura


      • Usually bright signals on T2 and FLAIR in the white matter


      • Postulated to represent sequelae of vasospasm, but could be the result of an underlying vascular disorder present in migraine patients


    • Aura without headache



      • May occur in patients with or without a history of migraine


      • Usually occur in an older age group


      • Visual symptoms most common, but can have motor, sensory, cognitive symptoms


      • Diagnosis of exclusion


    • Migraine and stroke



      • Increased risk of stroke in migraine with aura, mainly in women


      • Risk is exponentially increased with comorbid smoking and oral contraceptive agents


      • More often than not, infarction is not felt because of traditional atherosclerotic mechanisms


  • Treatment of migraine



    • General/behavioral



      • Exercise


      • Sleep


      • Stress reduction


      • Regular meals


      • Food analysis (limit caffeine, alcohol, monosodium glutamate, and so forth)


      • Limit medications and nicotine


    • Acute treatment



      • General considerations



        • Treat early in the course of the headache


        • Treat at least two headaches before giving up on a medication


        • Taylor treatment to speed of onset, presence of severe nausea, and so forth (i.e., pill vs. nasal spray vs. suppository vs. injection)


        • Restrict treatment to 2 to 3 days/week to limit rebound potential


      • Triptans



        • 5HT1b, 1d agonists (serotonin agonists)


        • 5HT1b activity correlates with efficacy


        • Increase serotonergic activity



        • Available in injection, nasal spray, pills, and orally disintegrating tablets


        • The most effective abortive therapy for migraine in existence


        • Should not be used in patients with coronary disease, cerebrovascular disease, Printzmetal angina, uncontrolled hypertension, basilar migraine, hemiplegic migraine


        • Use with caution in patients at risk of vascular disease


        • Common side effects: tingling, flushing, dizziness, chest and neck tightness, asthenia


        • General treatment response is 60% to 80%, with recurrence in about one third of patients


        • If one triptan is not effective, try others


        • Same recommendations regarding frequency of treatment also apply to triptans (prevention of rebound)


        • Triptan types



          • Imitrex (sumatriptan)—pill, NS (nasal spray), injection


          • Zomig (zolmitriptan)—pill, NS (nasal spray), ZMT oral dissolving formulation


          • Amerge (naratriptan)—pill


          • Maxalt (rizatriptan)—pill, MLT oral dissolving formulation


          • Axert (almotriptan)—pill


          • Frova (frovatriptan)—pill


          • Relpax (eletriptan)—pill


      • Ergotamines (also serotonin agonists)



        • DHE-45



          • Available intravenously, intramuscularly, nasally (Migranol)


          • Mainstay of treatment for intractable headache


          • “Cotton cocktail”—DHE, valium, intravenous compazine


          • “Raskin protocol”—intravenous DHE, preceded by antiemetic, sometimes followed by Valium


          • Check pregnancy test and electrocardiogram before first dose


      • Simple and combination analgesics and nonsteroidal anti-inflammatory drugs (NSAIDs)



        • For mild-to-moderate headache


        • Watch out for rebound and addiction


        • Adding metoclopramide or another antiemetic often increases efficacy


        • Examples: Midrin, Fioricet, Fiorinal, Wygesic, naproxen, ibuprofen


      • Opioids



        • Use for severe headache that is relatively infrequent


        • Watch for rebound, addiction


        • Use for “rescue” or to keep patients from going to emergency department (i.e., butorphanol nasal spray)


        • Use in patients with severe headache who are not triptan candidates


        • Consider signed “narcotic agreement”


      • Dopamine blockers (antiemetics) are effective for both headache and nausea



        • Metoclopramide, promethazine, prochlorperazine, odansetron, and so forth


        • Droperidol


        • Chlopromazine


      • Steroids—useful for intractable headache (such as oral prednisone taper, intravenous methylprednisolone or dexamethasone)



      • Other treatments



        • Nasal oxygen


        • Intravenous fluids


        • Intravenous valproate sodium


        • Indomethacin suppositories


        • Intravenous ketorolac


        • Antihistamines?


    • Preventive treatments



      • General principles



        • Consider if more than two headaches/month of significant severity, failure of acute therapies, overuse of acute meds, patient preference, and so forth


        • Start low and titrate to efficacy or side effects


        • Treat comorbidities with one agent when possible


        • May take 2 to 6 months for adequate trial


      • Antiepileptic agents



        • Divalproex sodium—most data from clinical trials


        • Topiramate


        • Gabapentin


        • Beta blockers—propranolol, nadolol, atenolol, timolol, metoprolol, and so forth


        • Calcium channel blockers—verapamil, flunarazine


      • Antidepressants



        • Tricyclics—amitriptyline (most effective), nortriptyline, doxepin, protriptyline,and so forth


        • SSRIs and SSNRIs—fluoxetine, paroxetine, sertraline, venlafaxine, and so forth


        • Serotonin antagonists—methysergide is no longer used much because of side effects


      • Monoamine oxidase inhibitors—rarely used because of side effects


      • Natural agents—feverfew, butterbur, magnesium, riboflavin, CoQ10


      • Muscle relaxants



        • Liorisal


        • Tizanidine


        • Botulinum toxin


      • Antipsychotics (such as quetiapine, olanzepine, risperidone)—some anecdotal reports of efficacy


  • Menstrual migraine



    • May occur before, during, or after menses


    • Occurs at time of greatest fluctuation of estrogen levels


    • Treatment



      • Abortive treatments the same


      • Short-term perimenstrual preventions—NSAIDS, ergots, triptans, Mg


      • Hormonal therapies



        • Oral contraceptive agents, conjugated estrogens, androgens, tamoxifen, gonadotropin-releasing hormone analogs


        • Help prevent estrogen level fluctuations


        • Hysterectomy and oophorectomy are not effective


        • Be careful with oral contraceptive agents in migraine with aura (stroke risk)


      • Dopamine agonists—bromocriptine



IV. Tension-Type Headache (TTH)



  • Epidemiology



    • One year prevalence: 28% to 63% of men in Western countries, 34% to 86% of women


    • More common in women


    • Peak prevalence, 20 to 50 years


    • Increased incidence in higher socioeconomic and educational groups


    • 60% of patients have diminished capacity for work


    • Genetic factors are present with multifactorial inheritance pattern for chronic tension type headache (CTTH)


  • Pathophysiology



    • Probably a clinical manifestation of abnormal neuronal sensitivity and pain facilitation


    • Abnormal modulation of interneurons, which connect the trigeminal nerves to motor neurons, associated with abnormal modulation by central pain centers


    • No correlation exists between muscle contraction or tenderness and headache severity


    • Nitric oxide may play a pathophysiologic role, as nitric oxide synthetase inhibitors reduce headache


    • Decreased pain threshold and decreased effectiveness of pain control systems (as in fibromyalgia)


    • Lower circulating catecholamines in TTH patients suggests decreased sympathetic activity


    • Increased GABA levels found in platelets of CTTH patients (? To counter neuronal hyperexcitability)


    • Sensitization of trigeminal nucleus caudalis occurs


  • Clinical features



    • Typically bilateral pressing or tightening, mild-to-moderate intensity, does not worsen with routine physical activity


    • No nausea or vomiting, but photophobia or phonophobia may be present


    • Headache lasts from 30 minutes to 7 days; may be continuous if CTTH


    • Pericranial tenderness may be present


    • Frontotemporal location most common


    • Associated neck or jaw discomfort common


    • Muscle tenderness and nodules often present


    • Lack of sleep is a precipitating factor


    • TTH is a risk factor for depression


  • Treatment

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Sep 8, 2016 | Posted by in NEUROLOGY | Comments Off on Pain

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