Korean J Pain.  2024 Oct;37(4):299-309. 10.3344/kjp.24171.

Methylcobalamin as a candidate for chronic peripheral neuropathic pain therapy: review of molecular pharmacology action

• Ramadhani A
• Astuti I
• Widiastuti MG
• Purwanti N

• KMID: 2559692
• DOI: http://doi.org/10.3344/kjp.24171

Abstract

Chronic peripheral neuropathic pain therapy currently focuses on modulating neuroinflammatory conditions. Methylcobalamin (MeCbl), a neuroregenerative agent, modulates neuroinflammation. This review aimed to explore the molecular pharmacology action of MeCbl as a chronic peripheral neuropathic pain therapeutic agent. MeCbl plays a role in various cellular processes and may have therapeutic potential in neurodegenerative diseases. Intracellular MeCbl modulates inflammation by regulating the activity of T lymphocytes and natural killer cells as well as secretion of inflammatory cytokines, namely, tumor necrosis factor-α, interleukin-6, interleukin-1β, epidermal growth factor, and neuronal growth factor. MeCbl can reduce pain symptoms in chronic neuropathic pain conditions by decreasing excitation and hyperpolarization-induced ion channel activity in medium-sized dorsal root ganglion (DRG) neurons and the expression of transient receptor potential ankyrin 1, transient receptor potential cation channel subfamily M member 8, phosphorylated p38MAPK, transient receptor potential cation channel subfamily V members 1 and 4 in the DRG, and the voltage-gated sodium channel in axons.

Keyword

Axons; Cytokines; Mecobalamin; Mononeuropathies; Neuralgia; Neurodegenerative Diseases; Neuroinflammatory Diseases; Neurons; Nervous System; Pain Management

Figure

• 

  Fig. 1 Chemical structure of methylcobalamin. The upper ligand consists of a methyl compound attached to a ring of cobalt. Modified from PubChem (https://pubchem.ncbi.nlm.nih.gov/compound/Methylcobalamin) [25].

• 

  Fig. 2 (A) A schematic mechanism of pathogenesis of peripheral neuropathic pain. Peripheral nerve injury activates macrophage in-situ to phagocytize myelin debris. Schwann cells differentiate into non-myelinating cells and phagocytize myelin debris along with macrophage. Cytokines and chemokines release from recruited circulatory neutrophil, macrophage, and T-cell (1). Neuron discharge of IL-1β, TNF-α, and IL-6 followed by histamine, serotonin (5-HT), Substance P, Bradykinin, and PG-E2 promotes peripheral and ganglion sensitization sequentially (2). Disruption in the remyelination process increase electrical activity, abnormal sensitivity to various stimulants, and abnormal contact between adjacent axons resulting in ephaptic cross-talk (3). (B) The action of MeCbl in modulating peripheral neuropathic pain. MeCbl reduces peripheral sensitization by regulating the NFKB activity of neutrophils, macrophages, and T-cells. MeCbl promotes remyelination by increasing the myelin binding protein expression and lipid synthesis of Schwann cells. MeCbl induces Ras protein methylation of neurons, enhancing the remyelination process. MeCbl regulates neuron's ion channel activation and controls peripheral and ganglionic sensitization. IL: interleukin, TNF: tumor necrosis factor, PG-E2: prostaglandin E2, MeCbl: methylcobalamin.

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