{"id":748,"date":"2020-02-17T21:38:34","date_gmt":"2020-02-17T16:08:34","guid":{"rendered":"https:\/\/medicineplexus.com\/?p=748"},"modified":"2020-02-17T21:38:34","modified_gmt":"2020-02-17T16:08:34","slug":"pharmacotherapy-of-neuropathic-pain","status":"publish","type":"post","link":"https:\/\/medicineplexus.com\/pharmacotherapy-of-neuropathic-pain\/","title":{"rendered":"Pharmacotherapy of Neuropathic Pain"},"content":{"rendered":"\n<p><strong>Pharmacotherapy of Neuropathic Pain<\/strong><\/p>\n\n\n\n<figure class=\"wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"467\" height=\"303\" src=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-289.png?w=467\" alt=\"\" class=\"wp-image-767\" srcset=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-289.png 467w, https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-289-300x195.png 300w\" sizes=\"(max-width: 467px) 100vw, 467px\" \/><\/figure>\n\n\n\n<p><strong>International Association for the Study of Pain&nbsp;\u2013 IASP definition<\/strong><\/p>\n\n\n\n<p><strong>Neuropathic pain <\/strong><strong>\u00e0 <\/strong>pain arising as a direct consequence of a lesion or disease affecting the somatosensory system<\/p>\n\n\n\n<ul><li><strong>global prevalence &#8211;<\/strong>1.5% and 8%.<\/li><li><strong>Causes of Neuropathic pain<\/strong><\/li><\/ul>\n\n\n\n<figure class=\"wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"411\" height=\"266\" src=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-290.png?w=411\" alt=\"\" class=\"wp-image-768\" srcset=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-290.png 411w, https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-290-300x194.png 300w\" sizes=\"(max-width: 411px) 100vw, 411px\" \/><\/figure>\n\n\n\n<figure class=\"wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"418\" height=\"196\" src=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-291.png?w=418\" alt=\"\" class=\"wp-image-769\" srcset=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-291.png 418w, https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-291-300x141.png 300w\" sizes=\"(max-width: 418px) 100vw, 418px\" \/><\/figure>\n\n\n\n<p><strong>Mechanism of NP<\/strong><\/p>\n\n\n\n<ul><li>All the causes mentioned &#8211; can trigger the release of inflammatory mediators- alters the properties of primary afferent neurons\u00e0<\/li><li>appearance of ectopic impulse because of increase in excitability and alterations in the properties of various types of Ca<sup>2+<\/sup> channels, voltage-gated Na+ and K+ channels and function of Na+-K+ ATPases, intracellular Ca<sup>2+<\/sup> handling and TRP channels<\/li><li>There are changes in synaptic transmission; excitatory synaptic processes are enhanced while inhibitory processes are attenuated.<\/li><\/ul>\n\n\n\n<p><strong>Mechanism of NP- Allodynia<\/strong><strong><\/strong><\/p>\n\n\n\n<ul><li>A\u03b4 and C-fibers carry information of noxious stimuli which synapse primarily onto dorsal horn neurons in laminae I and II whereas<\/li><li>A\u03b2 fibers carry tactile and innocuous (not harmful) information in laminae III and IV.<\/li><li>Normally these two are separated by GABAergic and glycinergic inhibition by suppressing the activity of pre-existing excitatory synaptic circuits<\/li><li>But post nerve injury there is attenuation of both these transmissions leading to abnormal processing of the sensory input<\/li><li>Hence, tactile information are processed as pain sensation.<\/li><\/ul>\n\n\n\n<p><strong>Symptoms of NP<\/strong><\/p>\n\n\n\n<p>Electric shock like sensation, numbness, stabbing, pins and needles, shooting, throbbing and burning sensation<\/p>\n\n\n\n<p>If untreated, the symptoms persist and have a <strong>propensity to become chronic.<\/strong><\/p>\n\n\n\n<p>The <strong>response to pain medications decreases in later stages.<\/strong><\/p>\n\n\n\n<p>Patients suffering from neuropathic pain frequently <strong>experience anxiety and sleep disturbances<\/strong>.<\/p>\n\n\n\n<p>Untreated chronic neuropathic pain can also lead to depression in patients as the quality of life is impaired. Thus, <strong>early screening is required<\/strong> to diagnose it and initiate appropriate treatment for effective management of patients experiencing neuropathic pain.<\/p>\n\n\n\n<p><strong>Screening tool for NP<\/strong><\/p>\n\n\n\n<p>Screening tools which <strong>combine self-reporting with physical examination<\/strong> are more accurate than those using self-reporting alone<\/p>\n\n\n\n<ul><li><strong>Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) Pain Scale<\/strong><\/li><li><strong>Douleur Neuropathique 4 (DN4) questionnaire<\/strong><\/li><li>Neuropathic Pain Questionnaire<\/li><li>pain DETECT<\/li><li>ID Pain<\/li><li>Neuropathic Pain Symptom Inventory<\/li><\/ul>\n\n\n\n<p><strong>Diagnosing neuropathic pain<\/strong><\/p>\n\n\n\n<ul><li>Bedside examination &#8211; to detect the thresholds of touch, pressure, heat, cold and vibration sensation<\/li><li>Pain diagram -pinpoint location of their pain<\/li><li>Visual analogue scale<\/li><\/ul>\n\n\n\n<figure class=\"wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"397\" height=\"297\" src=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-292.png?w=397\" alt=\"\" class=\"wp-image-770\" srcset=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-292.png 397w, https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-292-300x224.png 300w\" sizes=\"(max-width: 397px) 100vw, 397px\" \/><\/figure>\n\n\n\n<p><strong>Management of NP<\/strong><\/p>\n\n\n\n<ul><li>Treatment targeted to the specific diagnosis. Eg. &#8211; Control of Diabetes, removing offending drug , relieving compression<\/li><li>Pharmacotherapy- Start at lowest dose increase every 3 to 7 days to max tolerated dose<\/li><li>Behavioral Therapy, neuromodulation and psychological therapy.<\/li><\/ul>\n\n\n\n<p><strong>NeuPSIG guidelines<\/strong><\/p>\n\n\n\n<p>1<sup>st<\/sup> line \u2013 Gapabentin, Gabapentin ER\/enacarbil, Pregabalin, Duloxetine, Venlafaxine, TCAs<\/p>\n\n\n\n<p>2<sup>nd<\/sup> line &#8211; Capsaicin patches, Lidocaine patches, Tramadol<\/p>\n\n\n\n<p>3<sup>rd<\/sup> line &#8211; Botulinum toxin type A, Strong Opioids<\/p>\n\n\n\n<p><strong>Pregabalin<\/strong><\/p>\n\n\n\n<p>MOA- Act on the \u03b12\u03b4 subunit of voltage-gated calcium channels, which decrease central sensitization<\/p>\n\n\n\n<figure class=\"wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"388\" height=\"256\" src=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-293.png?w=388\" alt=\"\" class=\"wp-image-771\" srcset=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-293.png 388w, https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-293-300x198.png 300w\" sizes=\"(max-width: 388px) 100vw, 388px\" \/><\/figure>\n\n\n\n<p>Pregabalin blocks the VGCC and hence decrease glutamate and sensory neuropeptides (substance P and CGRP) release at synapse by decreasing Ca2+ influx. EAATs (excitatory amino acid transporters) activity is increased by pregabalin which caused more decrease in synaptic availability of glutamate. Decreased glutamate levels further inhibited the activation of NMDA and decreased the neuronal firing.&nbsp;<\/p>\n\n\n\n<p>Dose- started at 75-150 mg\/day, titrate to 300\u2013600 mg, in two divided doses<\/p>\n\n\n\n<p>Side effects &#8211;<\/p>\n\n\n\n<ul><li>* Dizziness (8% to 45%), somnolence (4% to 36%), ataxia (1% to 20%), headache (5% to 14%), fatigue (5% to 11%)<\/li><li>* Angioedema, peripheral edema<\/li><li>* Suicidal Behavior and Ideation<\/li><li>* Tremor<\/li><li>* Weight gain (3.7%)<\/li><li>* Blurred vision (4.8%), diplopia<\/li><li>Precaution- Reduce dose in patients with renal insufficiency<\/li><\/ul>\n\n\n\n<p><strong>Gabapentin<\/strong><\/p>\n\n\n\n<p>MOA- Act on the \u03b12\u03b4 subunit of voltage-gated calcium channels, which decrease central sensitization<\/p>\n\n\n\n<ul><li>Gabapentin 1200\u20133600 mg, in three divided doses.<\/li><li>Side effects- Sedation, dizziness, peripheral edema and weight gain<\/li><\/ul>\n\n\n\n<p><strong>TCA<\/strong><\/p>\n\n\n\n<p>Mechanism of action &#8211; serotonin and norepinephrine reuptake inhibitors &#8211;&nbsp; activate the descending inhibitory system<\/p>\n\n\n\n<p>Antidepressants increase noradrenaline via blocking of noradrenaline transporters at the terminal of the descending noradrenergic fiber from the locus coeruleus.<\/p>\n\n\n\n<p>Noradrenaline inhibits acute pain through \u03b1<sub>2<\/sub>-adrenergic receptors by pre-synaptic (inhibit neurotransmitters release) and post-synaptic (hyperpolarize cell membranes) mechanisms.<\/p>\n\n\n\n<ul><li>exert an analgesic action at doses lower than that required for antidepressant action, independently of their antidepressant action&nbsp;<\/li><li>Amitriptyline most widely used &#8211; doxepin , imipramine , nortriptyline , and desipramine also have been used.<\/li><li>Amitriptyline \/nortriptyline may be started at 10 mg\/d bedtime and slowly titrated up to an effective analgesic dose (eg, 75 mg\/d).<\/li><li>Side effects- Commonly reported AEs (generally anticholinergic): \u25e6 blurred vision \u25e6 cognitive changes \u25e6 constipation \u25e6 dry mouth \u25e6 orthostatic hypotension \u25e6 sedation \u25e6 sexual dysfunction \u25e6 tachycardia \u25e6 urinary retention<\/li><\/ul>\n\n\n\n<p><strong>SNRI<\/strong><\/p>\n\n\n\n<ul><li>Analgesic effect- attributed to activation of the descending pain inhibitory system by serotonin and noradrenalin.<\/li><li>Fewer side effects than TCAs<\/li><li>venlafaxine , duloxetine<\/li><li>Venlafaxine- 150-225mg\/day<\/li><li>Duloxetine \u2013 60 -120 mg \/day . Started at 30 mg\/day<\/li><li>ADR &#8211; nausea, somnolence, dry mouth, constipation, reduced appetite, diarrhea, hyperhidrosis, and dizziness,<\/li><\/ul>\n\n\n\n<p><strong>Opioids<\/strong><\/p>\n\n\n\n<p>Due to potential risk of abuse and concern about a recent increase in prescription opioid-associated overdose mortality, strong opioids are now recommended as third line of therapy.<strong><\/strong><\/p>\n\n\n\n<ul><li>Tramadol- \u03bc-Receptor agonist and monoamine reuptake inhibition<\/li><li>Morphine- \u03bc-Receptor agonist<\/li><li>Tramadol \u00e0Started at 50 mg once daily, and then titrated as tolerated. The effective dosage range is 200\u2013400 mg\/day.<\/li><li>Morphine \u00e0Individual titration<\/li><li>Side effects- Induces dizziness, dry mouth, nausea, constipation, and somnolence<\/li><\/ul>\n\n\n\n<p>NICE guidelines recommend tramadol only for use in rescue therapy on the basis that it was generally associated with higher rates of withdrawal due to adverse events compared with other treatments options<\/p>\n\n\n\n<p><strong>Lidocaine patch<\/strong><\/p>\n\n\n\n<ul><li>Lidocaine 5% &#8211; Sodium channel blockade<\/li><li>Up to 3 patches applied once daily directly over painful site for 12 h<\/li><li>Most appropriate for patients with well localized neuropathic pain and Allodynia<\/li><li>most common side effect: application-site sensitivity<\/li><\/ul>\n\n\n\n<p><strong>Capsaicin patch 8%<\/strong><\/p>\n\n\n\n<ul><li>Capsaicin is an irritating chemical found in chili peppers that causes burning pain upon contact with skin.<\/li><li>Immediately after topical application, it induces the release of substance P, which causes vasodilation and local irritation.<\/li><li>Upon chronic application, the nociceptive threshold is increased by depletion of substance P.<\/li><li><strong>Agonist of the transient receptor potential vanilloid receptor (TRPV1)<\/strong> and activates TRPV1 ligand-gated channels on nociceptive fibers<\/li><li>One to four patches to the painful area for 30-60 min every 3 months<\/li><li>Adverse effects local capsaicin-related reactions at the application site &#8211; pain, erythema, and sometimes edema and itching<\/li><li>potential risk of high blood pressure during treatment<\/li><\/ul>\n\n\n\n<p><strong>Botulinum toxin<\/strong><\/p>\n\n\n\n<ul><li>Botulinum toxin (BoNT) inhibits the release of pain mediators in peripheral nerve terminal, DRG, and spinal cord neuron, thereby reducing the inflammatory response and preventing the development of peripheral and central sensitization.<\/li><li>deactivates the sodium channel<\/li><li>Acetylcholine release inhibitor and neuromuscular-blocking agent.<\/li><li>50\u2013200 units to the painful area every 3 months<\/li><li>Side effects- Pain at injection site<\/li><\/ul>\n\n\n\n<p><strong>Behavioral therapy<\/strong><\/p>\n\n\n\n<ul><li>Cognitive behavioral therapy<\/li><li>Relaxation therapy<\/li><li>Psychotherapy and individual or group counseling<\/li><li>Acupuncture<\/li><li>Physical and occupational therapy<\/li><\/ul>\n\n\n\n<figure class=\"wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"480\" height=\"300\" src=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-294.png?w=480\" alt=\"\" class=\"wp-image-772\" srcset=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-294.png 480w, https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-294-300x188.png 300w\" sizes=\"(max-width: 480px) 100vw, 480px\" \/><\/figure>\n\n\n\n<p><strong>How to Select First-Line Treatment<\/strong><\/p>\n\n\n\n<ul><li>Although pregabalin and gabapentin have the same mechanism of action on the alfa2delta&nbsp; subunit of the presynaptic calcium channel, and randomized controlled trials showed that the two drugs have the same efficacy,<\/li><li>pregabalin has a linear pharmacokinetic profile, more favorable than gabapentin.<\/li><li>The&nbsp; pregabalin absorption after oral intake is not saturable and the bioavailability is virtually complete.<\/li><li>Therefore, in daily clinical practice, pregabalin is a better option than gabapentin.<\/li><\/ul>\n","protected":false},"excerpt":{"rendered":"<p>Pharmacotherapy of Neuropathic Pain International Association for the Study of Pain&nbsp;\u2013 IASP definition Neuropathic pain \u00e0 pain arising as a direct consequence of a lesion or disease affecting the somatosensory system global prevalence &#8211;1.5% and 8%. Causes of Neuropathic pain Mechanism of NP All the causes mentioned &#8211; can trigger the release of inflammatory mediators-[&#8230;]\n","protected":false},"author":3,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_seopress_robots_primary_cat":"","_seopress_titles_title":"","_seopress_titles_desc":"","_seopress_robots_index":"","footnotes":""},"categories":[3],"tags":[],"_links":{"self":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/posts\/748"}],"collection":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/comments?post=748"}],"version-history":[{"count":0,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/posts\/748\/revisions"}],"wp:attachment":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/media?parent=748"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/categories?post=748"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/tags?post=748"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}