Pharmacological treatment of chronic pain – the need for CHANGE

Varrassi, Giustino; Müller-Schwefe, Gerhard; Pergolizzi, Joseph V.; Orońska, Anna; Morlion, Bart; Mavrocordatos, Philippe; Margarit, César; Mangas, Cristina; Jaksch, W.; Huygen, Frank; Collett, Beverly; Berti, Marco; Aldington, Dominic; Ahlbeck, Karsten

doi:10.1185/03007991003689175

Cited by 137 publications

(115 citation statements)

References 81 publications

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“…3 This analgesia modulation represents a novel approach in a largely unmet therapeutic need. 4 Moreover, many studies have recently revealed novel potential pharmacological implications for TRPM8 modulators. For example, TRPM8 agonists have been proposed as useful diagnostic and therapeutic tools for the treatment of prostate cancer and benign prostate hyperplasia (BPH).…”

Section: Introductionmentioning

confidence: 99%

Tryptamine-Based Derivatives as Transient Receptor Potential Melastatin Type 8 (TRPM8) Channel Modulators

et al. 2016

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Pharmacological modulation of the transient receptor potential melastatin type 8 (TRPM8) is currently under investigation as a new approach mainly for the treatment of pain. In this study, a series of N-substituted tryptamines was prepared to explore the structural requirements determining TRPM8 modulation. As a result of a fluorescence-based screening assay, we identified two compounds acting as an activator (2-(1H-indol-3-yl)-N-(4-phenoxybenzyl) ethanamine, compound 21) or an inhibitor (N,N-dibenzyl-2-(1H-indol-3-yl) ethanamine, compound 12) of calcium influx in HEK293 cells. In patch-clamp recordings, compound 21 displayed a significantly higher potency (EC 50 = 40±4 µM) and a similar efficacy when compared to menthol; by contrast, compound 12 produced a concentrationdependent inhibition of menthol-induced TRPM8 currents (IC 50 = 367±24 nM). Molecular modelling studies using a homology model of a single TRPM8 subunit identified a putative binding site located between the VSD and the TRP box, disclosing two different binding modes for the agonist and the antagonist.

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Section: Introductionmentioning

confidence: 99%

Tryptamine-Based Derivatives as Transient Receptor Potential Melastatin Type 8 (TRPM8) Channel Modulators

et al. 2016

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“…Pharmacotherapy itself presents a challenge in chronic LBP, because of the difficulty in balancing adequate pain relief with acceptable tolerability, and the vicious circle of insufficient efficacy, leading to dose increase, which is followed by unacceptable tolerability, and thus dose reduction, and insufficient efficacy 27 . Adverse drug reactions (ADRs) 28 and lack of efficacy, as well as analgesic tolerance, drive the vicious circle and may contribute to treatment discontinuation.…”

Section: I a L D I S T R I B U T I O N U N A U T H O R I Z E D U S mentioning

confidence: 99%

Pharmacotherapy of low back pain: targeting nociceptive and neuropathic pain components

Morlion¹

2010

Current Medical Research and Opinion

110

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Vol. 27, No. 1, 2011, 11-33 To review pharmacological management of chronic low back pain (LBP), with respect to management of nociceptive and neuropathic components. Methods:Studies were identified by a PubMed search of English-language papers from the last 10 years, with additional hand searches of relevant reviews. Discussion:Paracetamol, non-steroidal anti-inflammatory drugs and cyclo-oxygenase-2 inhibitors target the nociceptive component of chronic LBP, and do not affect neuropathic pain mechanisms. Antidepressants target the neuropathic component of chronic LBP; however, conflicting efficacy results have been reported. Opioids target both nociceptive and to a lesser extent neuropathic pain. They are effective in chronic LBP, but many patients require higher doses or combination treatment. The long-term efficacy of opioids in chronic LBP has been questioned because of the absence of high-quality data and concerns regarding tolerability and dependence. The topical preparation lidocaine 5% plaster, indicated in post-herpetic neuralgia, is effective in localized neuropathic pain in patients with chronic LBP. Pregabalin is ineffective as monotherapy for chronic LBP but is effective when combined with celecoxib or opioids. Muscle relaxant monotherapy is ineffective in chronic LBP. Combination therapy is often necessary in patients with chronic LBP, in order to manage both nociceptive and neuropathic pain components. Conclusion:Chronic LBP often comprises both nociceptive and neuropathic components, therefore a multimodal and individualized treatment approach is necessary. Combining drugs with different mechanisms of action (e.g. an agent with m-receptor activity plus an agent of a different class) represents a rational approach to management of chronic LBP with both nociceptive and neuropathic components.

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“…Important measures necessary to achieving such improvement have been identified: the consensus group is committed to supporting research that will provide a better understanding of physicians' and patients' perspectives, to publishing study results, and to contributing to the education of healthcare professionals. This will ultimately increase the knowledge of pain mechanisms and facilitate treatment decisions 7 .…”

Section: Objectives Of the Change Pain Groupmentioning

confidence: 99%

“…The tendency then is for the clinician to increase the dose of analgesics, which increases sideeffects, so the dose is reduced, when pain relief again becomes inadequate, and so on. A 'vicious circle' may become established where the patient alternates between poor pain relief and avoidable side-effects 7 . Most pain specialists now agree that the balance between adequate pain relief and acceptable tolerability is best achieved, with fewest adverse effects, by matching the pharmacological action to the causative mechanisms involved 27 .…”

Section: Pain Treatment: Less Than Optimalmentioning

confidence: 99%

Make a CHANGE: optimising communication and pain management decisions

Müller-Schwefe

Jaksch

Morlion

et al. 2011

Current Medical Research and Opinion

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c i a l D i s t r i b u t i o n U n a u t h o r i z e d u s e p r o h i b i t e d . A u t h o r i s e d u s e r s c a n d o w n l o a d , d i s p l a y , v i e w a n d p r i n t a s i n g l e c o p y f o r p e r s o n a l u s eCurrent Medical Research & Opinion Vol. 27, No. 2, 2011, 481-488 Eli AlonUniversita¨tsspital Zurich, Switzerland Beverly CollettThe Pain Management Service, University Hospitals of Leicester, UK Dominic AldingtonChurchill Hospital, Oxford, UK AbstractThe major objectives of the CHANGE PAIN International Advisory Board are to enhance understanding of chronic pain and to develop strategies for improving pain management. At its second meeting, in November 2009, evidence was presented that around one person in five in Europe and the USA experiences chronic pain, and the delay before referral to a pain specialist is often several years. Moreover, physicians' pharmacological approach to chronic pain is inconsistent, as evidenced by the huge variation in treatment between different European countries. It was agreed that efficient communication between physician and patient is essential for effective pain management, and that efficacy/side-effect balance is a key factor in choosing an analgesic agent. The multifactorial nature of chronic pain produces various physical and psychological symptoms, so the management of chronic pain should be tailored to the individual. Pharmacological therapy must be matched to the causative mechanisms responsible, or it is likely to prove ineffective and risk the development of a 'vicious circle'; doses are increased because of inadequate pain relief, but this increases side-effects so doses are reduced, pain relief is then inadequate, so doses are increased, and so on. Pain management decisions should not therefore be based solely on the severity of pain. Based on the concept of individual treatment targets (ITT), the CHANGE PAIN Scale was adopted -a simple, user-friendly assessment tool to improve communication between physician and patient. The 11-point NRS enables the patient to rate the current pain intensity and to set a realistic individual target level. On the reverse are six key parameters affecting the patient's quality of life; clinicians simply need to agree with patients whether improvement is needed in each one. Regular use can establish the efficacy and tolerability of pain management, and the rate of progress towards individual treatment targets.

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Pharmacological treatment of chronic pain – the need for CHANGE

Cited by 137 publications

References 81 publications

Tryptamine-Based Derivatives as Transient Receptor Potential Melastatin Type 8 (TRPM8) Channel Modulators

Tryptamine-Based Derivatives as Transient Receptor Potential Melastatin Type 8 (TRPM8) Channel Modulators

Pharmacotherapy of low back pain: targeting nociceptive and neuropathic pain components

Make a CHANGE: optimising communication and pain management decisions

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