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Updated: Jan 10, 2026

The Sciatic Nerve Cuffing Model of Neuropathic Pain in Mice
Published on: July 16, 2014
Pyruvate kinase M2 - linked metabolic pathways in pain modulation
Vaishnavi Kalmegh1, Lahanya Guha2, Deep Rohan Chatterjee1
1Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research, Ahmedabad (NIPER-A), Gandhinagar, Gujarat, India.
Abstract:
The glycolytic enzyme pyruvate kinase M2 (PKM2) is emerging as a crucial modulator of cancer cell proliferation and pain signaling. Pathological lactate accumulation causes tissue acidification, sensitizing pain pathways, in which PKM2 plays a central role. Evidence links PKM2 to both nociceptive and neuropathic pain via molecular cascades involving cyclooxygenase (COX)-1/2, interleukin (IL)-1β, and extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) activation. Phosphorylated PKM2 enhances NFκB, STAT3, and ERK pathways, promoting inflammatory and neuronal sensitization. By integrating metabolic reprogramming with pain signaling, PKM2 represents a pivotal bridge between inflammation, neuronal excitation, and energy metabolism, offering promising therapeutic potential for managing complex pain-linked conditions.
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