Effects of Curcumin and Its Different Formulations in Preclinical and Clinical Studies of Peripheral Neuropathic and Postoperative Pain: A Comprehensive Review

Lesion or disease of the somatosensory system leads to the development of neuropathic pain. Peripheral neuropathic pain encompasses damage or injury of the peripheral nervous system. On the other hand, 10–15% of individuals suffer from acute postoperative pain followed by persistent pain after undergoing surgeries. Antidepressants, anticonvulsants, baclofen, and clonidine are used to treat peripheral neuropathy, whereas opioids are used to treat postoperative pain. The negative effects associated with these drugs emphasize the search for alternative therapeutics with better efficacy and fewer side effects. Curcumin, a polyphenol isolated from the roots of Curcuma longa, possesses antibacterial, antioxidant, and anti-inflammatory properties. Furthermore, the low bioavailability and fast metabolism of curcumin have led to the advent of various curcumin formulations. The present review provides a comprehensive analysis on the effects of curcumin and its formulations in preclinical and clinical studies of neuropathic and postoperative pain. Based on the positive outcomes from both preclinical and clinical studies, curcumin holds the promise of mitigating or preventing neuropathic and postoperative pain conditions. However, more clinical studies with improved curcumin formulations are required to involve its use as adjuvant to neuropathic and postoperative drugs.

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Topical Treatments and Their Molecular/Cellular Mechanisms in Patients with Peripheral Neuropathic Pain—Narrative Review

Pharmaceutics ◽

10.3390/pharmaceutics13040450 ◽

2021 ◽

Vol 13 (4) ◽

pp. 450

Author(s):

Magdalena Kocot-Kępska ◽

Renata Zajączkowska ◽

Joanna Mika ◽

David J. Kopsky ◽

Jerzy Wordliczek ◽

...

Keyword(s):

Neuropathic Pain ◽

Pain Management ◽

Clinical Studies ◽

Neuronal Cells ◽

Case Series ◽

Narrative Review ◽

Peripheral Sensitization ◽

Cellular Mechanisms ◽

Peripheral Neuropathic Pain ◽

Topical Treatments

Neuropathic pain in humans results from an injury or disease of the somatosensory nervous system at the peripheral or central level. Despite the considerable progress in pain management methods made to date, peripheral neuropathic pain significantly impacts patients’ quality of life, as pharmacological and non-pharmacological methods often fail or induce side effects. Topical treatments are gaining popularity in the management of peripheral neuropathic pain, due to excellent safety profiles and preferences. Moreover, topical treatments applied locally may target the underlying mechanisms of peripheral sensitization and pain. Recent studies showed that peripheral sensitization results from interactions between neuronal and non-neuronal cells, with numerous signaling molecules and molecular/cellular targets involved. This narrative review discusses the molecular/cellular mechanisms of drugs available in topical formulations utilized in clinical practice and their effectiveness in clinical studies in patients with peripheral neuropathic pain. We searched PubMed for papers published from 1 January 1995 to 30 November 2020. The key search phrases for identifying potentially relevant articles were “topical AND pain”, “topical AND neuropathic”, “topical AND treatment”, “topical AND mechanism”, “peripheral neuropathic”, and “mechanism”. The result of our search was 23 randomized controlled trials (RCT), 9 open-label studies, 16 retrospective studies, 20 case (series) reports, 8 systematic reviews, 66 narrative reviews, and 140 experimental studies. The data from preclinical studies revealed that active compounds of topical treatments exert multiple mechanisms of action, directly or indirectly modulating ion channels, receptors, proteins, and enzymes expressed by neuronal and non-neuronal cells, and thus contributing to antinociception. However, which mechanisms and the extent to which the mechanisms contribute to pain relief observed in humans remain unclear. The evidence from RCTs and reviews supports 5% lidocaine patches, 8% capsaicin patches, and botulinum toxin A injections as effective treatments in patients with peripheral neuropathic pain. In turn, single RCTs support evidence of doxepin, funapide, diclofenac, baclofen, clonidine, loperamide, and cannabidiol in neuropathic pain states. Topical administration of phenytoin, ambroxol, and prazosin is supported by observational clinical studies. For topical amitriptyline, menthol, and gabapentin, evidence comes from case reports and case series. For topical ketamine and baclofen, data supporting their effectiveness are provided by both single RCTs and case series. The discussed data from clinical studies and observations support the usefulness of topical treatments in neuropathic pain management. This review may help clinicians in making decisions regarding whether and which topical treatment may be a beneficial option, particularly in frail patients not tolerating systemic pharmacotherapy.

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ALIAmides Update: Palmitoylethanolamide and Its Formulations on Management of Peripheral Neuropathic Pain

International Journal of Molecular Sciences ◽

10.3390/ijms21155330 ◽

2020 ◽

Vol 21 (15) ◽

pp. 5330 ◽

Cited By ~ 2

Author(s):

Ramona D’Amico ◽

Daniela Impellizzeri ◽

Salvatore Cuzzocrea ◽

Rosanna Di Paola

Keyword(s):

Nervous System ◽

Neuropathic Pain ◽

Mast Cells ◽

Inflammatory Responses ◽

Bioactive Lipids ◽

Peripheral Neuropathic Pain ◽

Novel Approach ◽

Preclinical And Clinical Studies ◽

Somatosensory Nervous System

Neuropathic pain results from lesions or diseases of the somatosensory nervous system and it remains largely difficult to treat. Peripheral neuropathic pain originates from injury to the peripheral nervous system (PNS) and manifests as a series of symptoms and complications, including allodynia and hyperalgesia. The aim of this review is to discuss a novel approach on neuropathic pain management, which is based on the knowledge of processes that underlie the development of peripheral neuropathic pain; in particular highlights the role of glia and mast cells in pain and neuroinflammation. ALIAmides (autacoid local injury antagonist amides) represent a group of endogenous bioactive lipids, including palmitoylethanolamide (PEA), which play a central role in numerous biological processes, including pain, inflammation, and lipid metabolism. These compounds are emerging thanks to their anti-inflammatory and anti-hyperalgesic effects, due to the down-regulation of activation of mast cells. Collectively, preclinical and clinical studies support the idea that ALIAmides merit further consideration as therapeutic approach for controlling inflammatory responses, pain, and related peripheral neuropathic pain.

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In Vitro and In Vivo Effects of Flavonoids on Peripheral Neuropathic Pain

Molecules ◽

10.3390/molecules25051171 ◽

2020 ◽

Vol 25 (5) ◽

pp. 1171 ◽

Cited By ~ 7

Author(s):

Paramita Basu ◽

Arpita Basu

Keyword(s):

Neuropathic Pain ◽

Side Effects ◽

Nerve Injury ◽

Somatosensory System ◽

Present Review ◽

Common Symptom ◽

Murine Models ◽

Peripheral Neuropathic Pain

Neuropathic pain is a common symptom and is associated with an impaired quality of life. It is caused by the lesion or disease of the somatosensory system. Neuropathic pain syndromes can be subdivided into two categories: central and peripheral neuropathic pain. The present review highlights the peripheral neuropathic models, including spared nerve injury, spinal nerve ligation, partial sciatic nerve injury, diabetes-induced neuropathy, chemotherapy-induced neuropathy, chronic constriction injury, and related conditions. The drugs which are currently used to attenuate peripheral neuropathy, such as antidepressants, anticonvulsants, baclofen, and clonidine, are associated with adverse side effects. These negative side effects necessitate the investigation of alternative therapeutics for treating neuropathic pain conditions. Flavonoids have been reported to alleviate neuropathic pain in murine models. The present review elucidates that several flavonoids attenuate different peripheral neuropathic pain conditions at behavioral, electrophysiological, biochemical and molecular biological levels in different murine models. Therefore, the flavonoids hold future promise and can be effectively used in treating or mitigating peripheral neuropathic conditions. Thus, future studies should focus on the structure-activity relationships among different categories of flavonoids and develop therapeutic products that enhance their antineuropathic effects.

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722 EFFICACY OF FENTANYL HCL IONTOPHORETIC TRANSDERMAL SYSTEM (ITS) FOR ACUTE POSTOPERATIVE PAIN MANAGEMENT: A POOLED ANALYSIS OF FOUR CLINICAL STUDIES

European Journal of Pain ◽

10.1016/s1090-3801(06)60725-8 ◽

2006 ◽

Vol 10 (S1) ◽

pp. S188c-S189

Author(s):

I. Power ◽

S. Grond ◽

E.R. Viscusi

Keyword(s):

Pain Management ◽

Postoperative Pain ◽

Clinical Studies ◽

Postoperative Pain Management ◽

Pooled Analysis ◽

Acute Postoperative Pain ◽

Iontophoretic Transdermal System

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The effect of acute postoperative pain and chronic neuropathic pain on subsequent weight gain in the rat

Journal of Neurosurgery ◽

10.3171/2009.9.jns08136 ◽

2010 ◽

Vol 112 (4) ◽

pp. 780-783 ◽

Cited By ~ 2

Author(s):

James W. Leiphart ◽

Prasanna P. Vasudevan ◽

Samer R. Rajjoub ◽

Luis W. Dominguez ◽

Jason Chang

Keyword(s):

Neuropathic Pain ◽

Weight Gain ◽

Postoperative Pain ◽

The Other ◽

Acute Postoperative Pain ◽

Chronic Neuropathic Pain ◽

Postsurgical Pain ◽

Surgery Group ◽

The Difference ◽

Heat Hyperalgesia

Object Acute postoperative pain has demonstrated effects on appetite and weight gain in human studies. This study was designed to test the hypothesis that chronic neuropathic pain has a more significant effect on weight than acute postsurgical pain. Methods One hundred eighteen rats were separated into 3 groups: common sciatic nerve ligation, surgery without ligation, and no surgery. Each group was further divided to undergo testing at 3, 7, and 14 days. On the day of testing, the rats were tested for signs of pressure and heat hyperalgesia and were weighed. Results The effect on the percentage of change in body weight from the day of surgery to the day of testing was statistically significant for both the condition (F = 15.0, p < 0.0001) and the day of testing (F = 43.3, p < 0.0001). The rats that received no surgery had a change in weight of 2.3% on Day 3, 4.0% on Day 7, and 10.7% on Day 14. In the nonligation surgery group, the change was −3.8% on Day 3, 2.0% on Day 7, and 9.7% on Day 14. In the ligation surgery group, the change was −6.3% on Day 3, −0.7% on Day 7, and 4.9% on Day 14. This group began gaining weight by Day 14 but continued to have less weight gain than the other groups by Day 14. Conclusions Neuropathic pain inhibits weight gain more than normal, postsurgical pain. Recognizing the difference and initiating effective treatment for neuropathic pain may have an impact on the patient's nutrition.

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