PRODUCTMONOGRAPH Controls Pain Protects nerve Page 1 1 Neuropathic pain. PARTICULARS PAGE NO.NO.CONTENTS S. prevalence and causes 3-4 2 Neuropathic pain Pathophysiology 5 3 Pathogenesis of Diabetic Neuropathy 6 4 Management Of Neuropathic pain 7-8 5 Rationale of combination 9 6 Mechanism of Action of all ingredients 10 7 Competitors of Axinerve NP 11 8 Attached LBL 12 Controls Pain Protects nerve Page 2 . general introduction. anxiety. The international Association for the Study of Pain (IASP) defines NP as “pains resulting from disease or damage of the peripheral or central nervous systems and from dysfunction of the nervous system. Even with high prevalence in chronic conditions. There is no standard approach between health care providers for NP. Depression. and fall-related injury. Multiple sclerosis. and sleep disorders were significantly more prevalent in patients with neuropathic pain compared to without such pain. It has been shown that the about 26% of patients with type 2 diabetes can experience neuropathy. The Exact prevalence of neuropathic pain is not known.INTRODUCTION Neuropathic Pain is one of the most common types of pain. the overall numbers of NP conditions tends to be small. diagnosis. Cancer patients indicate a prevalence of 19–39. Global Scenario Diabetes has become one of the largest global health-care problems of the 21st century. reaching a pandemic level of 366 million people. but it is often under- recognized and undertreated. is the most common diabetic complication. One of the reasons is the lack of identification. Diabetic polyneuropathy (DPN). About 1% and 37% of chronic low back pain patients may have a neuropathic component related to it. Diabetic Neuropathy A global epidemic of diabetes mellitus has emerged and India leads the world with largest number of diabetic subjects earning the dubious distinction of being termed the “Diabetes capital of the world. DPN is a leading cause for disability due to foot ulceration and amputation. and spinal cord injury result in neuropathic pain in 8%. Stroke. gait disturbance. which has a lifetime prevalence of approximately 50%. The number of people with diabetes worldwide is predicted to double between 2000 and 2030. 7% and 67% of patients respectively. Pain continues after healing of rash in 8% of Herpes Zoster patients. Approximately 20 to 30% of patients with DPN suffer from neuropathic pain. and treatment. Controls Pain Protects nerve Page 3 . infectious Controls Pain Protects nerve Page 4 . medication like Isoniazid and thallium. the prevalence of neuropathy in India was 8. Beriberi (Vitamin B1).4% and this figure is significantly higher. Guillain- Barre Syndrome post.Indian Scenario The overall prevalence of neuropathy in a study with type 2 diabetic subjects is 19.1%. copper and arsenic. The Major Categories of Neuropathic Pain Toxic Chemo-radiation therapy in the treatment of cancer. Infectious Post Herpetic neuralgia. Autoimmune Chronic inflammatory demyelinating polyneuropathy and vasculitic neuropathy. HIV. Chagas disease (trypanosomes). Most of neuropathic conditions are not isolated to pure pain fibers and can coexist with inflammatory. Leprosy (mycobacterium). Neuropathic pain: Causes Neuropathic pain is due to myriad of disorders. According to recent study. Metabolic Diabetes. Trauma Phantom Limb syndromes and/or complex regional pain syndromes. Compressive Carpal tunnel syndrome and compartment syndromes. Alcohol induced neuropathy. exposure to chemical like lead. visceral and/or nociceptive pain as well as neuropathic dysfunction like autonomic nervous system involvement in diabetes. Lyme Disease (Spirochetes). This increased expression allows for decreased activation thresholds and increased membrane excitability. A pro-inflammatory milieu is created including cytokines. TNF alpha. Controls Pain Protects nerve Page 5 . chemokines. This spontaneous activity is thought to be related to an increase in voltage gated sodium channel expression. Central Sensitization Regular discharge from peripheral nerves causes release of excitatory neuropeptides and amino acids in the dorsal horn. substance P. This leads to phosphorylation of NMDA and AMPA receptors and expression of voltage gated sodium channels (similar to ectopic nerve activity). Spontaneous nerve activity has been shown in both the injured nerve as well as uninjured neighboring nerves. etc.Neuropathic Pain: Pathophysiology Ectopic nerve activity/Peripheral Sensitization This mechanism is responsible for pain sensed in the absence of external stimuli. Inflammatory reaction Inflammation results in activation of microglia in the nerve as well as the dorsal root ganglion. These factors facilitate neuropathic pain by further enhancing neuroexcitability. Pathogenesis of Diabetic Neuropathy The etiology and pathogenesis of diabetic neuropathy is multifaceted and attributed to the effects of hyperglycemia. and altered transport of nutrients within the nerve axons. accumulation of advanced glycation end products (AGEs) oxidative stress. Diabetes Mellitus Hyperglycemia Advanced glycation Polyol pathway Free radical generation Phosphokinase C end products activity and oxidative stress activity Vascular and neural dysfunction leading to complication Controls Pain Protects nerve Page 6 . tramadol. anticonvulsants. which are assessed with repeated requests to rate pain intensity. Several controlled studies have demonstrated that painful DPN can be relieved by antidepressants. Tricyclic antidepressants have long been used to treat all forms of neuropathic pain. Anticonvulsants and tricyclic antidepressants have emerged as mainstay of therapy. and blood pressure Rule out other causes of neuropathy* TCAs+ Nortriptyline (Pamelor. (TCAs = tricyclic antidepressants. opioids and topical application of capsaicin and recent meta-analysis support those findings. 300 mg at bedtime) or Controls Pain Protects nerve Page 7 . Many agents have been utilized and studied for treatment. 25 to 50 mg at bedtime) or Amitriptyline (25 to 150 mg at bedtime) Anticonvulsants Gabapentin (Neurontin.Management of Neuropathic Pain The aim of treatment is pain relief and functional rehabilitation. Reduction of pain by atleast 30% is clinically relevant. lipid levels.) Patient with diabetes mellitus and symmetric peripheral pain Initial evaluation Establish realistic goals for treatment Optimize glycemic control. Algorithm for treatment of diabetic peripheral Neuropathic pain. Thus a need exists for safe. To address this shortcoming. 200 to 600 mg twice per day) Serotonin-norepinephrine reuptake inhibitors Duloxetine (Cymbalta. Gabapentin (300 to 1. Controls Pain Protects nerve Page 8 . effective agents for painful DPN. 10 to 40 mg twice per day) Or Tramadol (Ultram. extended release (Effexor XR. 60 to 120 mg per day) Or Venlafaxine. combination of drugs acting through different mechanisms may produce improved pain relief. better- tolerated. 50 to 400 mg per day) Consider combination therapy with opiates Consider referral to pain specialist Only 20 to 40% reduction in pain intensity is achieved with current drugs.200 mg three times per day) or Pregabalin (Lyrica. 150 to 225 mg per day) Opiates Oxycodone. 50 to 200 mg three times per day) or Carbamazepine+ (Tegretol. controlled release (Oxycontin. Rationale of combining Nortriptyline with Pregabalin and Methylcobalamin Combination Current drugs reduce neuropathic pain and improve quality of life. pain and other symptoms in patient with fibromyalgia with an incomplete response to pregabalin treatment. A variety of medications (oral and Topical) are available for treating neuropathic pain. Remarkable reduction in pain intensity in PHN (Post Herpetic Neuralgia) as compared to pregabalin alone Adding Tricyclic antidepressant to pregabalin improve global status. Combining Pregabalin with Tricyclic antidepressant demonstrates larger pain reduction effects in spinal cord injury. however. Therapeutic benefits may include greater efficacy. Pregabalin and Nortriptyline are both the gold standards in treating neuropathic pain syndromes. Nortriptyline is the first line therapy for the treatment of neuropathic pain Synergize the effect of Pregabalin in treating Diabetic peripheral neuropathic Pain. Gabapentin and tricyclic antidepressants as first. Because of the failure of the existing painkillers to provide adequate relief. Controls Pain Protects nerve Page 9 . and guidelines have been published for its treatment.line therapy. Better safety and tolerability profile of Nortriptyline as compared to amitriptyline in elderly have been reported in Cochrane studies. Both of these guidelines recommend pregabalin. as single agents they are limited by incomplete efficacy and dose limiting adverse effects.for treating pain of diabetic neuropathy. there is a constant search for newer options. lower doses and fewer adverse effects. including two that have focused specifically on Neuropathic pain. Nortriptyline blocks the reuptake of noradrenaline and serotonin and resulting increased availability of these neurotransmitters at the synapse which may inhibit nociception by actions at spinal cord. Nortriptyline relieves pain by ameliorating insomnia & depression. brain stem or thalamic sites. With Nortriptyline pain relief may also be the result of opiate like actions on central neurons.Mechanism of Action of all active ingredients Nortriptyline Nortriptyline and Pregabalin are both the gold standards in treating neuropathic pain syndromes. Pregabalin Pregabalin binds subunits of voltage activated ca2+ channels leading to decrease ca2+ influx into nerve terminals and reduce the release of neurotransmitters including glutamate and NE. Controls Pain Protects nerve Page 10 . which covers and protects nerve fibers and thereby promotes myelination. Methylcobalamin Methylcobalamin works by functioning in the production of a material called myelin. Competitors For Axinerve NP Brand Name Company MRP GB 29 Total Corona 195 Finenerve-NT Akumentis 179 Nortipan M Medley 170 Dubinor Glenmark 130 Nervijen-NP Jenburkt 129 Controls Pain Protects nerve Page 11 . Front Back Controls Pain Protects nerve Page 12 .