Related Experiment Video
Updated: Jan 10, 2026
07:09
The Sciatic Nerve Cuffing Model of Neuropathic Pain in Mice
Published on: July 16, 2014
49.2K
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.
Drug Discovery Today
|November 25, 2025
Summary
Pyruvate kinase M2 (PKM2) links cancer cell growth and pain by altering metabolism and promoting inflammation. Targeting PKM2 offers potential for treating complex pain conditions.
Area of Science:
- Biochemistry
- Oncology
- Neuroscience
Background:
- Pyruvate kinase M2 (PKM2) is a glycolytic enzyme implicated in cancer cell proliferation.
- Pathological lactate accumulation, driven by PKM2, leads to tissue acidification and sensitizes pain pathways.
Purpose of the Study:
- To elucidate the role of PKM2 in pain signaling and its connection to metabolic reprogramming.
- To explore PKM2 as a therapeutic target for pain management.
Main Methods:
- Investigated molecular cascades involving PKM2, cyclooxygenase (COX)-1/2, interleukin (IL)-1β, and extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK).
- Examined the impact of phosphorylated PKM2 on inflammatory and neuronal sensitization pathways, including NFκB and STAT3.
Main Results:
- PKM2 plays a central role in both nociceptive and neuropathic pain.
- Phosphorylated PKM2 activates signaling pathways that promote inflammation and neuronal sensitization.
- PKM2 integrates metabolic reprogramming with pain signaling.
Conclusions:
- PKM2 acts as a critical link between inflammation, neuronal excitation, and energy metabolism.
- Targeting PKM2 presents a promising therapeutic strategy for complex pain-linked conditions.
Related Concept Videos
01:25Analgesia and Pain Management
1.5K
Pain is critical to various clinical pathologies, provoking an urgent need for effective management. Pain, whether acute or chronic, is a complex neurochemical process. Its alleviation depends on the type, with nonopioid analgesics effective for mild to moderate pain, such as musculoskeletal or inflammatory pain, while neuropathic pain responds best to anticonvulsants, tricyclic antidepressants, or serotonin/norepinephrine reuptake inhibitors. For severe acute or chronic pain, opioids may be...
1.5K
01:07MAPK Signaling Cascades
7.8K
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
7.8K
01:22PI3K/mTOR/AKT Signaling Pathway
5.3K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
5.3K
01:20Pain
1.2K
Pain serves as a critical warning signal that alerts the body to potential or actual harm. When mechanical pressure on the skin is intense, such as from a sharp pinch, the sensation transitions from touch to pain. Similarly, extreme temperatures, like a hot pot handle, convert the sensation of heat into pain. Pain can also result from overstimulation of other senses, such as blinding light, loud noise, or the intense heat from habañero peppers. This ability to sense pain is essential for...
1.2K
02:26NF-κB-dependent Signaling Pathway
9.7K
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
NF-κB-dependent Signaling Mechanism
The...
9.7K
03:03mTOR Signaling and Cancer Progression
4.6K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
4.6K