The ROS-Inflammation Loop That Keeps Chronic Pain Alive

If your pain has persisted or even worsened with no new injury to explain it, you are not imagining it. In this episode of our mitochondria series, Dr. Padda explains how overwhelmed cellular power plants leak a signal called reactive oxygen species that actively tells your nervous system to inflame and to hurt and how that signal can keep your pain system primed indefinitely. This article walks through that loop and how it can be interrupted.

How overwhelmed mitochondria leak a pain signal

Your mitochondria make energy by passing electrons down a series of steps called the electron transport chain. When everything is balanced, this runs cleanly. But when the chain gets backed up from too much fuel at once from high glucose, insulin resistance, or lipid overload the system jams. A jammed chain starts leaking electrons that react with oxygen to form unstable molecules called reactive oxygen species, or ROS. We usually picture ROS as simple damage, like rust or wear and tear. The deeper insight Dr. Padda highlights is that ROS also acts as a signaling molecule, a messenger and one of the things it signals is inflammation.

Why this turns up the pain you feel

ROS can switch on powerful inflammatory machinery inside your cells, including a complex called the NLRP3 inflammasome. This happens inside your nociceptors the pain-sensing nerves and inside glial cells, the immune-like support cells of your nervous system. When that machinery turns on, it releases inflammatory signals that prime your nervous system to be hyper-responsive to pain. Then a loop forms: ROS triggers inflammation, inflammation stresses the mitochondria further, the more impaired mitochondria leak even more ROS, and around it goes. This self-reinforcing cycle is a big part of why chronic pain so often becomes self-sustaining, persisting long after any original injury has healed. As Dr. Padda puts it, the loop has become the disease.

What a search for new damage can miss

When pain continues with no fresh injury on the scan, it can leave both patients and doctors baffled. But the absence of a new injury was never evidence that nothing is wrong it is a clue. A self-reinforcing loop of cellular stress and inflammation can keep your pain system lit up entirely on its own, with no new tissue damage to point to. Continuing to chase an injury that is not there can miss the actual driver. The encouraging difference is that a loop, unlike permanent damage, is something that can be interrupted.

How we work to break the loop at the Padda Institute

The approach Dr. Padda describes is to attack the loop at multiple points at once. We work to reduce the metabolic overload the high glucose, insulin resistance, and lipid excess that jams the electron transport chain and starts the ROS leaking in the first place. We aim to bolster your antioxidant defenses so the ROS that does form gets neutralized before it can signal, and we work to lower the systemic inflammation feeding the cycle from the other side. This is best understood as an investigational, whole-person approach to interrupting a self-reinforcing process, not a single quick fix. Individual results vary.

Frequently asked questions

Why does my chronic pain persist when there's no new injury?

Because pain can be driven by a self-reinforcing loop of cellular stress and inflammation rather than by fresh tissue damage. Overwhelmed mitochondria leak reactive oxygen species that switch on inflammatory machinery in your pain-sensing nerves and glial cells, keeping the nervous system primed. A loop like this can continue long after an original injury has healed. Individual results vary.

What are reactive oxygen species (ROS)?

Reactive oxygen species are unstable molecules formed when the mitochondria's electron transport chain gets backed up and leaks electrons. Beyond causing oxidative damage, ROS also acts as a signaling molecule that can activate inflammation inside pain-sensing nerves and glial cells. In chronic pain, that signaling helps keep the nervous system hyper-responsive.

Can antioxidant supplements fix this loop on their own?

Nothing in this discussion suggests any single supplement breaks the loop by itself; the described approach targets metabolic overload, antioxidant defenses, and systemic inflammation together. Antioxidant support is presented as one part of a broader plan, not a standalone cure. Do not start, stop, or change any medication or supplement without consulting your physician. Individual results vary.

Where are you located and how do I book?

Padda Institute Center for Interventional Pain Management, 4477 Woodson Rd, Suite 100, St. Louis, MO 63134. Book at painmd.tv/appointment/ or call (314) 481-5000.

Key takeaways

• Mechanism: jammed mitochondria leak ROS, which signals inflammation and primes pain-sensing nerves.
• Evidence status: ROS as a signaling molecule and NLRP3/glial roles in chronic pain are described as well established.
• Why timing matters: the ROS-inflammation loop is self-reinforcing and can keep pain lit up with no new injury.
• Next step: interrupting the loop at multiple points is the goal book at painmd.tv/appointment/.

Medically reviewed by Dr. Gurpreet Singh Padda, MD, MBA, MHP — Board Certified in Anesthesiology, Pain Medicine, Interventional Pain Management, Addiction Medicine, and Obesity Medicine. Last reviewed July 2026.

This article is educational and is not a substitute for evaluation, diagnosis, or treatment by a physician. Individual results vary. Do not start, stop, or change any medication without consulting your physician.

Dr. Gurpreet Singh Padda, MD, MBA, MHP