Cortical astrocytes rewire somatosensory cortical circuits for peripheral neuropathic pain

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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Discovery and Optimization of Highly Potent and Selective AT2R Antagonists to Relieve Peripheral Neuropathic Pain

ACS Omega ◽

10.1021/acsomega.1c01866 ◽

2021 ◽

Author(s):

Yanghui Guo ◽

Xiangui Huang ◽

Weiwei Liao ◽

Lichen Meng ◽

Daiwang Xu ◽

...

Keyword(s):

Neuropathic Pain ◽

Peripheral Neuropathic Pain

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The efficacy and safety profile of capsaicin 8% patch versus 5% Lidocaine patch in patients with diabetic peripheral neuropathic pain: a randomized, placebo-controlled study of south Asian male patients

Journal of Diabetes & Metabolic Disorders ◽

10.1007/s40200-021-00741-2 ◽

2021 ◽

Author(s):

Nadia Hussain ◽

Amira S. A. Said ◽

Farideh A. Javaid ◽

Amal Hussain Ibrahim Al Haddad ◽

Mudassir Anwar ◽

...

Keyword(s):

Neuropathic Pain ◽

South Asian ◽

Safety Profile ◽

Controlled Study ◽

Efficacy And Safety ◽

Peripheral Neuropathic Pain ◽

Male Patients ◽

Lidocaine Patch ◽

Asian Male

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

International Journal of Molecular Sciences ◽

10.3390/ijms22094666 ◽

2021 ◽

Vol 22 (9) ◽

pp. 4666

Author(s):

Paramita Basu ◽

Camelia Maier ◽

Arpita Basu

Keyword(s):

Neuropathic Pain ◽

Postoperative Pain ◽

Clinical Studies ◽

Curcuma Longa ◽

Somatosensory System ◽

Positive Outcomes ◽

Negative Effects ◽

Acute Postoperative Pain ◽

Peripheral Neuropathic Pain ◽

Preclinical And Clinical Studies

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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