What is neuropathic pain?

Neuropathic pain is a type of chronic pain that arises from damage or dysfunction of the nervous system. Unlike nociceptive pain, which is caused by tissue damage or inflammation, neuropathic pain results from abnormal processing of sensory signals by the nerves themselves.


Neuropathic pain can manifest in various ways and is often described as shooting, burning, tingling, stabbing, or electric shock-like sensations. It may be constant or intermittent, and it can occur spontaneously or be triggered by stimuli that would not normally cause pain, such as light touch or temperature changes.


Conditions that can cause neuropathic pain include:

  • Peripheral neuropathy: Damage to the peripheral nerves, often due to diabetes, infections, autoimmune diseases, or trauma.
  • Postherpetic neuralgia: Pain that persists after an episode of shingles (herpes zoster) due to damage to nerves affected by the virus.
  • Trigeminal neuralgia: Intense facial pain caused by irritation or damage to the trigeminal nerve, which supplies sensation to the face.
  • Diabetic neuropathy: Nerve damage caused by long-term high blood sugar levels in individuals with diabetes.
  • Spinal cord injury: Damage to the spinal cord resulting in persistent pain signals being sent to the brain.
  • Multiple sclerosis: A neurological condition that can lead to damage of the nerve fibers, causing neuropathic pain among other symptoms.


What is the relationship between neuropathic pain and oxidative stress?

The relationship between neuropathic pain and oxidative stress is an area of active research, and while the precise mechanisms are not fully understood, there is growing evidence to suggest that oxidative stress may play a role in the pathogenesis and maintenance of neuropathic pain. Here’s how neuropathic pain and oxidative stress are interconnected:


  • Nerve Damage: Neuropathic pain often arises from damage or dysfunction of the nerves, leading to abnormal transmission of pain signals. Nerve injury triggers a cascade of cellular events, including inflammation and oxidative stress. Injured nerves release pro-inflammatory cytokines and chemokines, which recruit immune cells to the site of injury and stimulate the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) by activating the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase enzyme complex and other sources.


  • Mitochondrial Dysfunction: Mitochondria, the cellular organelles responsible for energy production, are susceptible to oxidative damage. Mitochondrial dysfunction has been implicated in neuropathic pain, leading to impaired energy metabolism, increased production of ROS, and oxidative stress. Dysfunction of mitochondria may result from nerve injury, inflammation, or neurodegenerative processes associated with neuropathic pain conditions.


  • Oxidative Damage: Increased levels of oxidative stress markers, such as lipid peroxidation products, protein carbonyls, and DNA damage, have been observed in animal models and clinical studies of neuropathic pain. Oxidative damage to lipids, proteins, and nucleic acids can impair cellular function, disrupt signaling pathways, and contribute to neuroinflammation, neuronal hyperexcitability, and pain sensitization.


  • Neuroinflammation: Chronic neuroinflammation is a common feature of neuropathic pain conditions and is associated with the activation of microglia and astrocytes, release of pro-inflammatory cytokines and chemokines, and recruitment of immune cells to the site of nerve injury. Inflammatory mediators can stimulate the production of ROS and RNS by immune cells and neuronal cells, leading to oxidative stress and neuronal damage.


  • Peripheral Sensitization: Peripheral sensitization, characterized by increased excitability of nociceptive neurons in the peripheral nervous system, is a key mechanism underlying neuropathic pain. Oxidative stress has been implicated in the sensitization of nociceptive neurons, leading to enhanced responsiveness to painful stimuli and the development of neuropathic pain symptoms.


Overall, oxidative stress appears to be involved in the pathophysiology of neuropathic pain and may contribute to the development and maintenance of pain symptoms.