Neuropathic pain strategies to improve clinical outcome
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Neuropathic pain strategies to improve clinical outcome

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  • Peripheral neuropathy is commonly associated with diabetes mellitus. It can also present as post herpetic neuralgia. In addition, there are several other conditions associated with the symptoms of painful neuropathy. We will be focusing this discussion on postherpetic neuralgia and diabetic neuropathic pain.
  • Neuropathic pain affects a significant proportion of the world's population. Neuropathic pain is not a single entity or diagnosis.It represents a variety of syndromes such as painful diabetic neuropathy (PDN), trigeminal neuralgia and post herpetic neuralgia (PHN), which probably have different neural mechanisms and demonstrate different responses to pharmacologic and nonpharmacologic treatments. Over the last decade, our understanding of the basic mechanisms contributing to the generation of neuropathic pain has greatly improved. Together with the completion of the various genome sequencing projects and significant advances in micro array and target validation strategies, new therapeutic approaches are being rigorously pursued.
  • Development of allodynia in neuropathic pain The mechanisms of neuropathic pain are different because both small and large diameter afferent fibers are involved. In neuropathic pain dynamic allodynia is mediated by A- beta-fibres and the static type of neuropathic pain involves small diameter nociceptive fibres. Calcium channels are heterogeneously distributed among the medium sized neurons. This heterogeneity may provide specificity not only to sensory functions but also to sensory responses following nerve injury. Nerve injury may result in altered alpha(2)delta subunit expression in spinal cord and dorsal root ganglia and that this change may play a role in neuropathic pain processing. The analgesic effect of Pregabalin on neuropathic pain is mediated, at least in part, by its peripheral inhibitory action on the impulse generation of ectopic discharges caused by nerve injury. Central mechanisms Following a peripheral nerve injury, anatomical and neuro–chemical changes can occur within the central nervous system (CNS) that can persist long after the injury has healed. This "CNS plasticity" may play an important role in the evolution of chronic, neuropathic pain. As is the case in the periphery, sensitization of neurons can occur within the dorsal horn following peripheral tissue damage and this is characterized by an increased spontaneous activity of the dorsal horn neurons, a decreased threshold and an increased responsiveness to afferent input, and cell death in the spinal dorsal horn. The allodynia and hyperalgesia associated with neuropathic pain may be best explained by: 1) The development of spontaneous activity of afferent input 2) The sprouting of large primary efferents (eg. A–beta fibers from lamina 3 into lamina 1 and 2) 3) Sprouting of sympathetic efferents into neuromas and dorsal root and ganglion cells 4) Elimination of intrinsic modulatory systems 5) Up regulation of receptors in the dorsal horn which mediate excitatory processes. At the cellular level, the central nervous system plastic changes appear to be associated with enhanced neurotransmission via the NMDA receptor. Under the appropriate conditions, appropriate C–fiber stimulation can activate dorsal horn inter–neurons, causing them to release excitatory amino acids (eg. aspartate and glutamate), which will excite wide dynamic range (WDR) neurons via the NMDA receptor. NMDA receptor activation triggers a cascade of events leading to sensitization of dorsal horn wide dynamic range neurons then ensues. There is a significant increase in intracellular calcium and activation of protein kinases and phophorylating enzymes and release of excitatory amino acids and neuropeptides from primary afferent pain fibers. Peripheral sensitization Neuropathic pain, in contrast to nociceptive pain(sharp, aching, throbbing, or gnawing), is described as "burning", "electric", "tingling", and "shooting" in nature. It can be continuous or paroxysmal in presentation. Neuropathic pain is produced by damage to, or pathological changes in the peripheral or central nervous systems. In addition to sensitization following damaged peripheral nerves, the formation of ectopic neuronal pacemakers can occur at various sites along the length of the nerve. Increased densities of abnormal or dysfunctional sodium channels are thought to be the cause of this ectopic activity. Adrenergic receptor sensitivity develops in an area of damage. Neuropeptides are released. The nerve trunk becomes a source of ectopic impulse generation, and sympathetic activity can produce pain. This is the peripheral mechanism. New treatment options for the management of neuropathic pain are specially designed to modulate these pathogenic mechanisms.Pregabalin is a new drug which affects the altered alpha 2 delta subunit expression of calcium channels by acting as an alpha 2 delta subunit ligand.
  • The diagnosis of painful neuropathy can be made based on the clinical presentation of the patient, the past history and of course based on the results of several investigations adopted appropriately. One important distinguishing feature of neuropathic pain is that it is often worse at night unlike muscular pain which is worse during the day with the increase in the level of activity . Inflammatory pain on the other hand is worse first thing in the morning and during activity.
  • Heightened awareness of typical characteristics, makes identification of neuropathic pain fairly easy.
  • Examination should always include inspection of the painful body part and comparison with the contralateral side for color, temperature, skin texture, sensation, and weakness. Documentation of a neurological deficit in the distribution of pain helps build a case for neuropathic pain syndrome. Anesthesia dolorosa is one of the hallmarks of neuropathic pain. It occurs either because of automatic firing of higher-order neurons in the pain transmission pathway or because larger-diameter sensory nerves are damaged (causing numbness) but C-fiber nociceptors are still able to send pain signals The presence of allodynia (i.e., pain from a nonnoxious stimulus, such as light touching or rubbing) also suggests a neuropathic process. Sympathetically mediated pain is associated with autonomic changes in tissues, including cooling of the skin, abnormalities of vascular tone, increased sweating and neurogenic edema. In a patient who presents with a swollen limb that is redder and also cooler than the contralateral limb, a neurogenic process (rather than inflammation) should be suspected. Subacute herpetic neuralgia that does not progress to PHN may reflect peripheral tissue damage and inflammation caused by a particularly severe or widespread rash Asymmetric neuropathies in diabetic patients should be investigated for entrapment neuropathy Clinical impressions suggest that neuropathic pain is often worse at night and significantly impairs sleep.
  • We will be discussing 2 common types of neuropathic pain, namely: 1.Postherpetic neuralgia 2.Diabetic neuropathic pain
  • The increased incidence of Varicella zoster has led to an increase in the incidence of post herpetic neuralgia. The increased prevalence of diabetes mellitus and other immunocompromized states is perhaps responsible for the increased incidence of Herpes zoster.
  • The elderly are at a greater risk of Herpes zoster. Recurrent attacks are seen in about 6% of the patients.
  • Women and the elderly are at a greater risk. Greater the severity of the rash greater is the likelihood of the occurrence of post herpetic neuralgia later. So also, the presence of a prodromal syndrome also increases the risk of Herpes zoster.
  • Distal symmetric polyneuropathy the most common type of diabetic neuropathy, is an anatomically diffuse process primarily affecting sensory and autonomic fibers, although minor distal motor findings may be present in advanced cases. The longest nerves are affected first, with symptoms typically beginning insidiously in the toes and then advancing proximally up the legs. As the disease progresses, symptoms begin in the fingertips and eventually affect the thorax and abdomen; it always advances proximally. Both small and large-diameter fiber sensory neurons are involved, although the earliest manifestations may be primarily small-fiber. Involvement of small-fiber sensory neurons may result in loss of normal pain and temperature sensation which can predispose the patient to injury, ulceration, and chronic infection. These patients may experience neuropathic pain manifesting itself as a burning sensation, sharp, shooting pains, or deep aching. Large sensory fiber degeneration leads to loss of vibratory and proprioceptive sensation, which is not clinically significant until the neuropathy is advanced. In addition, these patients have absent or reduced deep tendon reflexes and slowed nerve conduction velocities. Numbness, tingling, and a sensation of tightness in the extremity are commonly associated with sensory polyneuropathy. Nocturnal exacerbation of neuropathic symptoms (NENS) is a recognized symptom of diabetic peripheral neuropathy (DPN). NENS, especially if affected by body position, or if accompanying a pattern of walking limitation should lead to suspicion of spinal stenosis. Positional testing should be considered in possible cases. Quantitative sensory testing of small nerve fiber function is a useful test to detect the presence of neuropathy, and overall diabetic patients with neuropathic pain have more sensory loss. However, small nerve fiber abnormalities detected by quantitative sensory testing do not predict the presence of pain in diabetic neuropathy. Asymmetric neuropathies in diabetic patients should be investigated for entrapment neuropathy. One might also see Focal and Multifocal neuropathies : Truncal radiculopathy usually occurs in middle-aged patients, often in those who have relatively mild diabetes. Onset of pain usually is acute and the pain may be located in the back, chest, or abdomen. There may be an accompanying area of sensory loss or dysesthesia. Limb mononeuropathies are particularly common in persons with diabetes and may occur on the basis of focal ischemia, entrapment, compression, or trauma to superficially placed nerves, such as the median nerve (as in the carpal tunnel syndrome), the ulnar nerve and the peroneal nerve.
  • Corneal confocal microscopy for the early detection of diabetic peripheral neuropathy. Principle: Nerve fiber tortuosity may indicate a degenerative and attempted regenerative response of nerve fibers to diabetes. Confocal microscopy appears to allow early detection of beginning neuropathy, because decreases in nerve fiber bundle counts precede impairment of corneal sensitivity. Place in therapy: Corneal confocal microscopy allows rapid, noninvasive in vivo evaluation of corneal nerve tortuosity. Corneal confocal microscopy accurately defines the extent of corneal nerve damage and repair and acts as a surrogate measure of somatic neuropathy in diabetic patients. It could represent an advance to define the severity of neuropathy and expedite assessment of therapeutic efficacy in clinical trials of human diabetic neuropathy. Laser Doppler flowmetry It provides a non-invasive means for evaluating microcirculating disturbances in diabetes, long before the initial clinical presentation of peripheral arterial occlusive disease or diabetic foot.
  • An accurate diagnosis is important in order to treat the underlying condition. Symptomatic relief of pain will serve in improving the quality of life of the patients suffering from neuropathic pain.
  • Several treatment options are available for the management of neuropathic pain. These drugs act at different sites along the pain transmission pathways. Therefore if one were to use 2 drugs which act at different sites along the pain axis, a synergistic analgesic effect would be observed.
  • Several treatment options are available for the management of neuropathic pain. These drugs act at different sites along the pain transmission pathways. Therefore if one were to use 2 drugs which act at different sites along the pain axis, a synergistic analgesic effect would be observed.
  • Combination therapy with drugs acting at different sites along the pain pathway would be beneficial in patients suffering from neuropathic pain. The choice of drugs will have to be made based on the balance between the efficacy and the side effect profile of the drug.
  • Pregabalin is a new drug that has been shown to be effective for treating partial epilepsy and peripheral neuropathic pain in clinical trials. Pregabalin, an alpha2-delta ligand with analgesic, anxiolytic and anticonvulsant activity.Pregabalin has demonstrated efficacy in relieving pain associated with post herpetic neuralgia, diabetic peripheral neuropathy and trigeminal neuralgia in several studies.
  • It is a structural, but not functional, analogue of GABA. It acts as a ligand of the alpha2- delta subunit, a protein associated to the voltage-dependent calcium channels. Pregabalin is a higher-potency and more effective analogue of gabapentin that acts as a potent ligand for this site. Calcium channel blockers are substances used for treating high blood pressure and coronary heart disease. New medications have been developed that modulate calcium channels but also show promise in psychiatric and neurological applications. Pregabalin binds to a subunit of calcium channels--the alpha2delta receptors--thereby reducing calcium influx to neurons. As a result, less glutamate is released from nerve endings that use excitatory amino acids as transmitters. This in turn reduces substance P-related activation of heteroreceptors on noradrenergic synapses, total transmitter release, and finally neuronal activity. That mechanism is the probable explanation for the usefulness of Pregabalin in the treatment of neuropathic pain and for its possible anticonvulsant and anxiolytic effects. .
  • Pregabalin acts as a ligand at the alpha2 subunit of the calcium channels. These channels are up regulated after a nerve injury. By acting at these channels, Pregabalin can inhibit the release of glutamate which leads to a reduction of neurotransmission and thus brings about relief of neuropathic pain.
  • Pregabalin is more potent than gabapentin due to its greater affinity at the alpha 2 subunit of the delta receptors.
  • Pregabalin can be given at lower doses than gabapentin because of : 1.Its excellent bioavailability 2.Higher potency Secondly Pregabalin is not metabolized in the liver. Hence the chances of drug interactions occurring are very low. Special patient populations: Renal insufficiency patients Pregabalin is eliminated unchanged in urine. Hence the dose should be reduced in patients with even moderate renal failure (creatinine clearance below 60 ml/min). Hepatic insufficiency patients Pregabalin is not metabolized in the liver. Hence it can be safely given in patients with hepatic insufficiency.
  • Pregabalin is generally well tolerated. The side effects observed are of a mild intensity and are short lived .
  • Pregabalin is generally well tolerated. The side effects observed are of a mild intensity and are short lived .
  • Greater affinity for the alpha 2 subunit of calcium channels Clinical implication: A lower dose of pregabalin will be required to treat the patient compared to gabapentin Better oral bioavailability Clinical implication: A lower dose of pregabalin will be required to treat the patient compared to gabapentin More potent than gabapentin Clinical implication: Pregabalin achieves efficacy at lower doses No pharmacokinetic variability Clinical implication: There are lesser chances of inter -individual variability with pregabalin as compared to gabapentin Favorable pharmacokinetics( no drug interactions) Clinical implication: These features of pregabalin allow rapid dose escalation when titration of doses is required Greater therapeutic index Clinical implication: Pregabalin has fewer dose related adverse effects.
  • Study Design: Double-blind, randomized placebo-controlled study Patient population: 370 patients with PHN Treatment given: Pregabalin 150, 300, or 600 mg/day bid or Placebo. Duration of treatment : 13-weeks Assessment of Efficacy: Primary Efficacy end point : Mean pain score from daily pain diaries. Secondary Efficacy measures : Mean sleep-interference score from daily sleep diaries and Patient Global Impression of Change (PGIC). RESULTS: Pregabalin provided significant, dose-proportional pain relief as compared to the placebo treated patients Weekly mean pain scores significantly improved as early as week 1. Sleep interference in all Pregabalin groups was also significantly improved at endpoint, compared with placebo (p < 0.001), beginning at week 1 (p < 0.01). At study termination, patients in the 150 (p = 0.02) and 600 mg/day (p = 0.003) groups reported better global improvement than those in the placebo group. CONCLUSIONS: Pregabalin, dosed BID, provided sustained relief of neuropathic pain associated with PHN and was well tolerated.
  • Pregabalin in diabetic neuropathic pain FEATURES Study design : Randomized, double-blind, multi center study. Patient population : Two hundred forty-six men and women with painful diabetic neuropathy Treatments given : Pregabalin 150 or 600 mg/day by mouth or placebo. Duration of treatment : 6-weeks Assessment of Efficacy : Primary Efficacy end point : Mean pain score at the end of treatment RESULTS Pregabalin 600 mg/day significantly decreased mean pain score to 4.3 vs 5.6 for placebo (P = .0002) and increased the proportion of patients who had a > or =50% decrease from baseline pain (39% vs 15% for placebo, P = .002 ). CONCLUSIONS These study results show pregabalin 600 mg/day to be safe and effective in reducing the pain and other associated symptoms of painful diabetic neuropathy.
  • Pregabalin also significantly reduced sleep interference, past week and present pain intensity, sensory and affective pain scores, and body pain and decreased by > or =50% the number of patients describing their pain as gnawing, sickening, fearful, and punishing and cruel. More patients receiving pregabalin 600 mg/day than placebo showed improvement, as rated on the Clinical and Patient Global Impression of Change scales, 73% vs 45% and 85% vs 47%, respectively. CONCLUSIONS These study results show Pregabalin 600 mg/day to be safe and effective in reducing the pain and other associated symptoms of painful diabetic neuropathy.
  • Pregabalin caused a significant improvement in all the parameters of Health Related Quality of Life tested.
  • Pregabalin has a rapid onset of action. The pain relief it provides has been found to reduce sleep interference.

Neuropathic pain strategies to improve clinical outcome Neuropathic pain strategies to improve clinical outcome Presentation Transcript

  • Neuropathic Pain : Strategies to Improve Clinical OutcomeBrought to you by : One is the most independent, unconventional and individualistic of all numbers
  • Common conditions associated with neuropathic painDiabetes Peripheral neuropathy Mononeuropathy RadiculopathyHerpes zoster Radiculopathy (dermatome)Spine surgery RadiculopathyHIV infection or Peripheral neuropathyAIDS Mononeuropathy Radiculopathy MyelopathyAlcoholism with Peripheral neuropathyneuropathy MononeuropathyAmputation Neuroma Phantom limb
  • Neuropathic pain• Not a single entity or diagnosis• Represents a variety of syndromes • Painful diabetic neuropathy • Trigeminal neuralgia • Post-herpetic neuralgia• Improved understanding of the basic mechanisms Whatever the Mind can conceive and Believe, the mind can Achieve Napoleon Hill
  • Neuropathic pain: Pathogenesis• Altered alpha-2 delta subunit expression of calcium channels• Central sensitization NMDA receptor activation• Peripheral sensitization: formation of ectopic impulsesNew treatment options modulate these mechanisms. e.g. Pregabalin •Ann Pharmacother. 2005 Dec;39(12):2029-37. Epub 2005 Nov 15. •Psychopharmacology (Berl). 2005 Dec;183(2):133-43. Epub 2005 Nov 9 .
  • Diagnostic pointersDistinguishing the type of pain through clinical history• Neuropathic pain: Often worse at night• Muscular pain: Usually worse during the day when activity is increased• Inflammatory pain: Worse first thing in the morning and during activity
  • Diagnosis based on the typical characteristics of neuropathic pain• The presence of certain accompanying conditions (e.g. diabetes, HIV or herpes zoster infection, multiple sclerosis)• Pain described as shooting, stabbing, lancinating, burning, or searing• Pain worse at night• Pain following anatomic nerve distribution• Pain in a numb or insensate site
  • Clues from the examination of the patient reporting neuropathic pain• Neurological deficit in the distribution of pain• Anesthesia dolorosa• Presence of allodynia• A swollen limb that is redder and also cooler than the contralateral limb, a neurogenic process (rather than inflammation)
  • Two Most Important Neuropathies• Post herpetic neuralgia• Diabetic neuropathy related pain
  • Post-herpetic Neuralgia• Varicella-zoster virus is a re-emerging infection Acute pain that accompanies Herpes zoster usually subsides spontaneously, but in 10% of patients the pain persists and intensifies• The incidence of Post-herpetic neuralgia increases up to 50% amongst elderly patients Acta Chir Iugosl. 2004;51(4):53-7.
  • Herpes zoster• Approximately 50% of individuals reaching 90 years of age will have had HZ• In approximately 6% of the patients, a second attack may occur (usually several decades after the first) Expert Opin Pharmacother. 2004 Mar;5(3):551-9.
  • Risk Factors for PHN• Old age• Female gender• Presence of a prodrome• Severe rash Neurology. 2004 May 11;62(9):1545-51. Science is below the mind; Spirituality is beyond the mind
  • Startling Facts of Treatment of PHN• Lidocaine patch 5% gives relief of pain and tactile allodynia• Corticosteroids give neither reliable protection from appearance of postherpetic neuralgia, nor shorten its duration???• Pre-emptive treatment with low-dose tricyclics (ami- or nor-triptyline 10-25 mg nocte) from the time of diagnosis of acute shingles reduces the incidence of postherpetic neuralgia by about 50% Drugs. 2004;64(9):937-47. When they tell you to grow up, they mean stop growing
  • Acyclovir treatment• Treatment of herpes zoster with 800 mg/d of oral acyclovir within 72 hours of rash onset may reduce the incidence of residual pain at 6 months by 46% in immunocompetent adults Arch Intern Med. 1997 Apr 28;157(8):909-12. Of a burning and unremitting character - F.W.PAVY
  • Diabetic Neuropathy • The prevalence : 7.5% in newly diagnosed diabetics when the definition is restricted to symptomatic subjects who have abnormalities on neurological examination • The prevalence increases with the duration of diabetes, so that 25 years after the initial diagnosis of diabetes, the prevalence is 50%Three is the most playful of all numbers and also creative, inspirationaland motivating
  • Diabetic Neuropathy• Distal symmetric polyneuropathy• Longest nerves are affected first• The earliest manifestations may be primarily small- fiber• As the disease progresses, symptoms begin in the fingertips and eventually affect the thorax and abdomen; it always advances proximally• Nocturnal exacerbation of neuropathic symptoms (NENS) Diabet Med. 2005 Dec;22(12):1763-5 Postgrad Med J. 2006 Feb;82(964):95-100 “Men of Genius Admired: Men of Wealth envied women of power feared but only women of character are trusted” A- Friedman
  • Recent advances in diagnosis of neuropathy• Corneal confocal microscopy• Laser Doppler flowmetry Invest Ophthalmol Vis Sci. 2004 Feb;45(2):418-22. Invest Ophthalmol Vis Sci. 2000 Sep;41(10):2915-21 Take time to think; it is the source of power Take time to read; it is the foundation of wisdom Take time to work; it is the price of
  • Neuropathic Pain: Approach to Treatment• Diagnosis• Treat underlying condition/Symptomatic treatment• Reduce pain• Improve physical function• Reduce psychological distress• Improve QoLNine is the most humanitarian of all numbers. It is effort and sacrifice withoutthe need for reward.
  • Site of action of drugs used for neuropathic pain BRAIN Descending Modulation Anticonvulsants C Opioids N Tricyclic Antidepressant / Selective nor epinephrine S reuptake inhibitor Central Sensitization Anticonvulsants SPINAL Opioids PNS CORD NMDA – ReceptorPeripheral AntagonistsSensitization Tricyclic Antidepressant / Anticonvulsants Selective nor epinephrine Opioids reuptake inhibitor Topical Analgesics Local anesthetics Tricyclic Antidepressant “By Nature All Men/ Women are alike but by Education widely different” - Chinese
  • Site of action of drugs used for neuropathic pain BRAIN Descending Modulation Anticonvulsants C Opioids N Tricyclic Antidepressant / Selective nor epinephrine S reuptake inhibitor Central Sensitization Anticonvulsants SPINAL Opioids PNS CORD NMDA – ReceptorPeripheral AntagonistsSensitization Tricyclic Antidepressant / Anticonvulsants Selective nor epinephrine Opioids reuptake inhibitor Topical Analgesics Local anesthetics Tricyclic Antidepressant “By Nature All Men/ Women are alike but by Education widely different” - Chinese
  • Management of neuropathic painPatient diagnosed with neuropathicpainStart treatment with the first line drugsIn case of no response after 3 monthsDrugs from a second drug class may betried Try combination therapy“Serious, sincere, systematic study surely secures supremesuccess”
  • Pregabalin• A new neuromodulator for neuropathic pain.• An alpha 2-delta ligand• A structural analogue of GABA• Analgesic, anxiolytic and anticonvulsant activity “The Truth is fear and immorality are two of the greatest inhibitors of Performance to progress”
  • Pregabalin: Mechanism of action • Acts as a ligand of the alpha2- delta subunit of calcium channels. • Decreased calcium entry into nerve endings • Less glutamate released from nerve endings Relief of neuropathic painIt is not your position that makes you happy or unhappy it is your disposition
  • Site of action of Pregabalin Nerve injuryAltered alpha (2) delta subunit expression in spinal cord and dorsal root ganglia Site of action of Pregabalin Neuropathic pain processing As one is common to all numbers, it is often seen as the origin of all things
  • Pregabalin and Gabapentin• Pregabalin is a more effective analogue of gabapentin• Pregabalin has a higher potency at the alpha 2 delta subunit of calcium channelsTwo symbolizes partnership implying that accomplishments are best through coordination.
  • Pregabalin Pharmacokinetics• Absorption: Almost 100%• PPB: None• Metabolism: Not metabolized in the liver• Excretion: Urine• Half-life: 6 hours• Clinical Implications: Effective at lower dose No drug interactionsHate screeches, fear squeals; conceits trumpets but love sings lullabies
  • Dose of Pregabalin• Initial dose : 75 mg bd or 50 mg tds• Can be increased to 300 mg/day in 1 week• Can be increased to a maximum dose of 300 mg bd or 200 mg tds after 2-4 weeks if required A good teacher is a perpetual learner
  • Side Effects Pregabalin is usually well tolerated • CNS: dizziness and drowsiness • General: Weight gain in the elderlyThree can be seen in the divisions of a human in mind, body and spirit
  • Side Effects Pregabalin is usually well tolerated • CNS: dizziness and drowsiness • General: Weight gain in the elderlyThree can be seen in the divisions of a human in mind, body and spirit
  • Pregabalin vs Gabapentin • Greater affinity for the alpha 2 subunit of calcium channels : Effective at lower doses • Better oral bioavailability: Effective at lower doses • More potent than gabapentin: Effective at lower doses • No pharmacokinetic variability : Lesser chances of inter -individual variability • Favorable pharmacokinetics: No drug interactions • Greater therapeutic index: Lesser ADR“Motivation is the Spark that lights the Fire of Knowledge and fuels the engine of Accomplishment
  • Clinical Experience with Pregabalin in Neuropathic PainPregabalin in Post-herpetic neuralgia(PHN)• Significant dose-proportional pain relief• Rapid and sustained pain relief• Reduced interference with sleep• Improves QoL• Well tolerated Curr Med Res Opin. 2006 Feb;22(2):375-84.Learn to adapt, adjust and accommodateLearn to give, not to take and learn to serve not to rule
  • Pregabalin in Diabetic Neuropathic Pain 50%% Patients with 50% reduction of pain scores from baseline 45% 40% 39% 35% 30% 25% 20% 15% 15% 10% 5% 0% Pregabalin Placebo In all of us, even in good men, there is a wild - beast nature which peers out in sleep
  • Clinician’s and Patient’s rating of Pregabalin 90% 85% 80% 73% 70% %Patients reporting improvement 60% 47% 50% 45% 40% 30% 20% 10% 0% Pregabalin Placebo“Knowledge can be communicated but not Wisdom” - Hermann Hesse
  • Pregabalin Effects on Health Related Quality of Life (QoL)• Significantly reduced weekly mean sleep interference scores• Improvement in the mental health domain• Body pain and vitality domains were improved in the 300 mg/day group• Decreased sleep interference and significant improvements in health related QoL (Quality of Life) measures Pain. 2004 May;109(1-2):26-35.At twenty the will rules At thirty the intellect At forty the Judgment
  • PREGABALIN: Salient Effects in Neuropathic Pain • Rapid and sustained analgesic action • Significantly improves slow-wave sleep • Reduces neuropathic pain of post herpetic neuralgia and diabetic neuropathy • Improves health related QoL (Quality of Life) • Well tolerated • Has a low discontinuation rateFour is reliable, punctual, systematic and dependable, doing what it says it will do.
  • CONCLUSIONSuccessful therapy of neuropathic pain basedon :• Accurate diagnosis• Right choice of drugs• Ability to maintain the QoL of the patient Time and Words cannot be recalled - Fuller
  • THANK YOU