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Review
. 2020 Jun 9:14:478.
doi: 10.3389/fnins.2020.00478. eCollection 2020.

Exploring the Promise of Flavonoids to Combat Neuropathic Pain: From Molecular Mechanisms to Therapeutic Implications

Md Sahab Uddin  1   2 , Abdullah Al Mamun  1   2 , Md Ataur Rahman  3 , Md Tanvir Kabir  4 , Saad Alkahtani  5 , Ibtesam S Alanazi  6 , Asma Perveen  7 , Ghulam Md Ashraf  8   9 , May N Bin-Jumah  10 , Mohamed M Abdel-Daim  5   11
Affiliations
Review

Exploring the Promise of Flavonoids to Combat Neuropathic Pain: From Molecular Mechanisms to Therapeutic Implications

Md Sahab Uddin et al. Front Neurosci. .

Abstract

Neuropathic pain (NP) is the result of irregular processing in the central or peripheral nervous system, which is generally caused by neuronal injury. The management of NP represents a great challenge owing to its heterogeneous profile and the significant undesirable side effects of the frequently prescribed psychoactive agents, including benzodiazepines (BDZ). Currently, several established drugs including antidepressants, anticonvulsants, topical lidocaine, and opioids are used to treat NP, but they exert a wide range of adverse effects. To reduce the burden of adverse effects, we need to investigate alternative therapeutics for the management of NP. Flavonoids are the most common secondary metabolites of plants used in folkloric medicine as tranquilizers, and have been claimed to have a selective affinity to the BDZ binding site. Several studies in animal models have reported that flavonoids can reduce NP. In this paper, we emphasize the potentiality of flavonoids for the management of NP.

Keywords: GABA; benzodiazepines; flavonoids; neuronal injury; neuropathic pain.

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Figures

FIGURE 1
FIGURE 1
The outlines of the mechanism of neuropathic pain from nerve damage with probable clinical interventions. Nerve damage leads to peripheral nerve injury as well as spinal cord injury (central). The peripheral sensitization and hyperexcitability take place due to the peripheral nerve injury. Furthermore, the hyperexcitability of peripheral nociceptor leads to the generation of ectopic impulses, which plays a crucial role in producing spontaneous pain, superficial pain, and paroxysmal pain that ultimately leads to neuropathic pain. Conversely, selective sodium (Na) channel blockers such as lidocaine and carbamazepine inhibit the generation of ectopic impulses that reduces the sensation of neuropathic pain. On the other hand, the hyperexcitability of the central dorsal horn is caused by spinal cord injury that subsequently decreases intraspinal inhibitory interneurons, which finally leads to neuropathic pain. However, GABA agonists, including baclofen, inhibit the decreased intraspinal inhibitory interneurons that plays an essential role in reducing the sensation of neuropathic pain. DRG, dorsal root ganglion; Na, sodium.
FIGURE 2
FIGURE 2
Basic structure of flavonoids and their sub-classes.
FIGURE 3
FIGURE 3
Effects of flavonoids on different neuropathic pain models.
FIGURE 4
FIGURE 4
Effects of flavonoids on peripheral neuropathy. Flavonoids act on different peripheral neuropathic pain conditions by blocking oxidative stress, activation of glial cells, and mitochondrial dysfunction. PARP, poly-ADP ribose polymerase.
See this image and copyright information in PMC

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