This slide illustrates the concept that many different underlying causes of neuropathic pain may express as different spontaneous and stimulus-evoked pain symptoms via different pathophysiological mechanisms. The key talking points on this slide are as follows: There are many possible causes of neuropathic pain. Neuropathic pain is commonly classified according to the etiological nature of the damage to the nervous system or the anatomical distribution of the pain, although the relationship between etiology, mechanisms, and symptoms/signs is highly complex. For instance, the pain caused by diverse diseases may originate through common mechanisms also one mechanism could be responsible for many different symptoms conversely, the same symptom in 2 patients may be caused by different mechanisms furthermore, more than one mechanism can operate in a single patient, and the pattern of mechanisms and symptoms within a single patient may change with time. No pain pathophysiological mechanism is an inevitable consequence of a particular disease process. Studies are needed to further define pathophysiological mechanisms of neuropathic pain. Reference Woolf and Mannion. Lancet 1999;353:1959-64 Additional key words: pathophysiology
This slide describes the type of pain associated with the two broad categories of neuropathic pain signs and symptoms: spontaneous (also termed stimulus-independent) and stimulus-evoked symptoms. The key talking points on this slide are as follows: Spontaneous pain is the most frequent symptom in all painful neuropathies and presents with a burning quality, localized superficially, or electric shock-like pain for several seconds. Dysesthesias are abnormal sensations that are unpleasant, and include shooting, lancinating (piercing/stabbing) or burning pains. Paresthesias are abnormal sensations that are not unpleasant, such as tingling. Symptoms of stimulus-evoked pain can be described according to the nature of the provoking stimulus, i.e. whether it is usually pain-free and innocuous, or painful and noxious. Allodynia is a painful response to a stimulus that is not normally painful. Hyperalgesia is a heightened response to a stimulus that would normally evoke pain. Hyperpathia is a painful syndrome characterized by an abnormally delayed painful reaction to a stimulus, especially a repetitive stimulus. References Baron. Clin J Pain. 2000;16:S12-S20. Merskey H et al. (Eds) In: Classification of Chronic Pain: Descriptions of Chronic Pain Syndromes and Definitions of Pain Terms. 1994:209-212.
Management of Painful Neuropathy
Neuropathic PainPain initiated or caused by aprimary lesion or dysfunctionin the nervous systemClassification of Chronic PainInternational Association for the Study ofPain, 1994
Types of Neuropathic Pain•Peripheral Neuropathy •Central NeuropathyDue to anatomical, chemical or Due to pathophysiologicalbiochemical changes to peripheralnerves changes in the brain or spinal chord i.e. the primaryExamples include: lesion is in the CNS•diabetic neuropathy•sciatica, Examples include:•post-surgery•Fibromyalgia •phantom limb pain•post-herpetic neuralgia, •Pain following stroke•trigeminal neuralgia, •multiple sclerosis•compression by a tumour•radiation therapy•Chemotherapy (e.g. vincristine)•pain in HIV infections
Most Common Neuropathic Painful Conditions1. Radiculopathy – Cervical Radiculopathy: Restricted motion in neck; pain in neck and arms – Lumbosacral Radiculopathy: Commonly, low back pain and sciatica2. Fibromyalgia3. Post traumatic nerve compression4. Post herpetic neuralgia5. Diabetic peripheral neuropathy6. Trigeminal neuralgia7. Phantom limb pain8. Pain following stroke9. Multiple sclerosis
Analog of GABA, binds to alpha 2 delta subunit of voltagegated calcium channels.
• Novel evidence suggest that regulation of…• Glutamate.• Substance P & Noradrenalin.• Results is relief from neuro - pathic pain syndrome.
Partial Onset SeizuresDiabetic Peripheral Neuropathy Post Herpetic Neuralgia Fibromyalgia
Comparative Pharmacokinetics Pregabalin GabapentinFDA Approved DPN, Fibromyalgia, PHN, PHN, EpilepsyIndications Partial SeizuresMechanism of Selectively bind to the alpha2- Selectively bind to the alpha2-deltaAction delta subunit of Ca+ channel subunit of Ca+ channelPharmacokinetic Linear (plasma concentration is Non-linear (plasma concentrationprofile dose proportionate) increases disproportionately to dose)Oral bioavailability > 90% all doses 60% 900mg 47% 1200mg 34% 2400mg 33% 3600mgDosing BID TIDTime to Effective 1 day (effective starting dose > 9days (titrate to effective dose ofdose of 150mg/day) 1800mg/d)
Clinically Evidence•The efficacy of Gablin (pregabalin) for the management ofneuropathic pain associated with DM•4 double-blind, fixed-dose, placebo controlled, multi-centerstudies with twice a day (BID) and 3 times a day (TID) dosing•Studies DPN1, DPN2, DPN3 and DPN4 enrolled a total of 1124patients with type 1 or 2 diabetes mellitus with painful distal symmetrical sensorimotor polyneuropathy for1 to 5 years
Spinal Cord Injury “The literature data suggest that Gablin (Pregabalin) is more efficacious thanGabapentin in many important variables for Neuropathic pain in Spinal Cord Injury” Eur J Clin Pharmacol. 2008 Jul 8
FDA APPROVED DOSAGE SCHEDULE• … Initial Dose in …• … Diabetic Peripheral Neuropathy• … Post Herpetic Neuralgia• … Partial Onset of Seizures• … Fibromyalgia• … Is 75mg Twice daily• … Maximum daily recommended dose is … 600mg per day.
Recommended DosageDosing Parameter Low Back Pain Sciatica Spinal Cord Injury Initial Daily 75mg 2 times 75mg 2 times daily 75mg 2 times daily daily (150mg/day) (150mg/day) Dosage (150mg/day)Maximum Daily Dosage 600mg/day 600mg/day 600mg/day