The neuropathic pain market

Nightingale, Sarah

doi:10.1038/nrd3624

Cited by 58 publications

(32 citation statements)

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“…The most commonly studied neuropathic pain subtypes include diabetic neuropathic pain (DNP), postherpetic neuralgia (PHN), and HIV-related neuropathic pain. Collectively, these three conditions were estimated to affect over six million people across the seven major pharmaceutical markets (USA, UK, Japan, France, Germany, Spain, and Italy) in 2010 (Nightingale, 2012) However, the total affected population is considerably larger owing to the number of additional off-label uses, such as neuropathic lower back pain, cancer-related neuropathic pain, complex regional pain syndrome and postoperative neuropathic pain.…”

Section: Introductionmentioning

confidence: 99%

Current Status of the New Antiepileptic Drugs in Chronic Pain

Sidhu

Sadhotra

2016

Front. Pharmacol.

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Antiepileptic drugs (AEDs) are extensively used worldwide to treat a wide range of disorders other than epilepsy, such as neuropathic pain, migraine, and bipolar disorder. Due to this situation more than 20 new third-generation AEDs have been introduced in the market recently. The future design of new AEDs must also have potential to help in the non-epileptic disorders. The wide acceptance of second generation AEDs for the management of various non-epileptic disorders has caused the emergence of generics in the market. The wide use of approved AEDs outside epilepsy is based on both economic and scientific reasons. Bipolar disorders, migraine prophylaxis, fibromyalgia, and neuropathic pain represent the most attractive indication expansion opportunities for anticonvulsant developers, providing blockbuster revenues. Strong growth in non-epilepsy conditions will see Pfizer’s Lyrica become the market leading brand by 2018. In this review, we mainly focus on the current status of new AEDs in the treatment of chronic pain and migraine prophylaxis. AEDs have a strong analgesic potential and this is demonstrated by the wide use of carbamazepine in trigeminal neuralgia and sodium valproate in migraine prophylaxis. At present, data on the new AEDs for non-epileptic conditions are inconclusive. Not all AEDs are effective in the management of neuropathic pain and migraine. Only those AEDs whose mechanisms of action are match with pathophysiology of the disease, have potential to show efficacy in non-epileptic disorder. For this better understanding of the pathophysiology of the disease and mechanisms of action of new AEDs are essential requirement before initiating pre-clinical and clinical trials. Many new AEDs show good results in the animal model and open-label studies but fail to provide strong evidence at randomized, placebo-controlled trials. The final decision regarding the clinical efficacy of the particular AEDs in a specific non-epileptic disorder should be withdrawal from randomized placebo trials rather than open-label studies; otherwise this may lead to off-label uses of drug. The purpose of the present review is to relate the various mechanisms of action of new AEDs to pathophysiological mechanisms and clinical efficacy in neuropathic pain and migraine.

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Section: Introductionmentioning

confidence: 99%

Current Status of the New Antiepileptic Drugs in Chronic Pain

Sidhu

Sadhotra

2016

Front. Pharmacol.

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“…Furthermore, chronic neuropathic pain can persist for months, without the underlying cause being treatable or identifiable. Indeed, only one in four patients experience over 50 per cent pain relief [36]. No single target has been shown to be uniquely associated with the establishment of neuropathic pain.…”

Section: The Many Facets Of Endocannabinoidsmentioning

confidence: 99%

“…The activation of microglia and astrocytes in the dorsal horn of the spinal cord plays a critical role in the development of facilitated nociceptive responses and spinal hyper-excitability in chronic pain models [35]. Chronic pain and neuropathic pain are indications for which there is high unmet need in the clinic [36]. Furthermore, chronic neuropathic pain can persist for months, without the underlying cause being treatable or identifiable.…”

Section: The Many Facets Of Endocannabinoidsmentioning

confidence: 99%

Endocannabinoids in nervous system health and disease: the big picture in a nutshell

Skaper

Marzo²

2012

Phil. Trans. R. Soc. B

102

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The psychoactive component of the cannabis resin and flowers, delta9-tetrahydrocannabinol (THC), was first isolated in 1964, and at least 70 other structurally related 'phytocannabinoid' compounds have since been identified. The serendipitous identification of a G-protein-coupled cannabinoid receptor at which THC is active in the brain heralded an explosion in cannabinoid research. Elements of the endocannabinoid system (ECS) comprise the cannabinoid receptors, a family of nascent lipid ligands, the 'endocannabinoids' and the machinery for their biosynthesis and metabolism. The function of the ECS is thus defined by modulation of these receptors, in particular, by two of the best-described ligands, 2-arachidonoyl glycerol and anandamide (arachidonylethanolamide). Research on the ECS has recently aroused enormous interest not only for the physiological functions, but also for the promising therapeutic potentials of drugs interfering with the activity of cannabinoid receptors. Many of the former relate to stress-recovery systems and to the maintenance of homeostatic balance. Among other functions, the ECS is involved in neuroprotection, modulation of nociception, regulation of motor activity, neurogenesis, synaptic plasticity and the control of certain phases of memory processing. In addition, the ECS acts to modulate the immune and inflammatory responses and to maintain a positive energy balance. This theme issue aims to provide the reader with an overview of ECS pharmacology, followed by discussions on the pivotal role of this system in the modulation of neurogenesis in the developing and adult organism, memory processes and synaptic plasticity, as well as in pathological pain and brain ageing. The volume will conclude with discussions that address the proposed therapeutic applications of targeting the ECS for the treatment of neurodegeneration, pain and mental illness.

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“…As there remains a tremendous need for new medications to treat chronic pain conditions (Nightingale, 2012), we tested whether this compound would reduce nociceptive behavior in the chronic constriction injury (CCI) model of neuropathic pain, as well as in the carrageenan model of inflammatory pain. Each of these assays is highly sensitive to the antinociceptive effects of orthosteric CB 1 agonists and inhibitors of endocannabinoid catabolic enzymes (Lichtman et al, 2004;Russo et al, 2007;Kinsey et al, 2009;Ghosh et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

A Cannabinoid CB1 Receptor-Positive Allosteric Modulator Reduces Neuropathic Pain in the Mouse with No Psychoactive Effects

Ignatowska‐Jankowska

Baillie

Kinsey

et al. 2015

Neuropsychopharmacol

139

180

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The CB 1 receptor represents a promising target for the treatment of several disorders including pain-related disease states. However, therapeutic applications of Δ 9 -tetrahydrocannabinol and other CB 1 orthosteric receptor agonists remain limited because of psychoactive side effects. Positive allosteric modulators (PAMs) offer an alternative approach to enhance CB 1 receptor function for therapeutic gain with the promise of reduced side effects. Here we describe the development of the novel synthetic CB 1 PAM, 6-methyl-3-(2-nitro-1-(thiophen-2-yl)ethyl)-2-phenyl-1H-indole (ZCZ011), which augments the in vitro and in vivo pharmacological actions of the CB 1 orthosteric agonists CP55,940 and N-arachidonoylethanolamine (AEA). ZCZ011 potentiated binding of [ 3 H]CP55,940 to the CB 1 receptor as well as enhancing AEA-stimulated [35 S]GTPγS binding in mouse brain membranes and β-arrestin recruitment and ERK phosphorylation in hCB 1 cells. In the whole animal, ZCZ011 is brain penetrant, increased the potency of these orthosteric agonists in mouse behavioral assays indicative of cannabimimetic activity, including antinociception, hypothermia, catalepsy, locomotor activity, and in the drug discrimination paradigm. Administration of ZCZ011 alone was devoid of activity in these assays and did not produce a conditioned place preference or aversion, but elicited CB 1 receptor-mediated antinociceptive effects in the chronic constriction nerve injury model of neuropathic pain and carrageenan model of inflammatory pain. These data suggest that ZCZ011 acts as a CB 1 PAM and provide the first proof of principle that CB 1 PAMs offer a promising strategy to treat neuropathic and inflammatory pain with minimal or no cannabimimetic side effects.

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The neuropathic pain market

Cited by 58 publications

References 0 publications

Current Status of the New Antiepileptic Drugs in Chronic Pain

Current Status of the New Antiepileptic Drugs in Chronic Pain

Endocannabinoids in nervous system health and disease: the big picture in a nutshell

A Cannabinoid CB1 Receptor-Positive Allosteric Modulator Reduces Neuropathic Pain in the Mouse with No Psychoactive Effects

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