Pain chronic after injury, surgery due to neuroinflammation
Pain is a protective physiological response to injury but it is dysfunctional when it persists after a normal period of repair. Research just published in the Scandinavian Journal of Pain describes how neuroinflammation due to dysregulated glial cells (immune cells in the central nervous system) cause chronic persistent neuropathic pain. The authors state:
"Acute pain in response to injury is an important mechanism that serves to protect living beings from harm. However, persistent pain remaining long after the injury has healed serves no useful purpose and is a disabling condition. Persistent postsurgical pain, which is pain that lasts more than 3 months after surgery, affects 10–50% of patients undergoing elective surgery...When established, this type of pain is difficult to treat and new approaches for prevention and treatment are needed."
Activated glial cells promote chronic pain
They set out to investigate the role of inflammatory glial cell dysfunction based on observing...
"A possible contributing mechanism for the transition from acute physiological pain to persistent pain involves low-grade inflammation in the central nervous system (CNS), glial dysfunction and subsequently an imbalance in the neuron–glial interaction that causes enhanced and prolonged pain transmission."
Their investigation brought these mechanisms to light:
"Immediately after an injury to a nerve ending in the periphery such as in surgery, the inflammatory cascade is activated and immunocompetent cells migrate to the site of injury. Macrophages infiltrate the injured nerve and cause an inflammatory reaction in the nerve cell. This reaction leads to microglia activation in the central nervous system and the release of pro-inflammatory cytokines that activate and alter astrocyte function. Once the astrocytes and microglia have become activated, they participate in the development, spread, and potentiation of low-grade neuroinflammation. The inflammatory activated glial cells exhibit cellular changes, and their communication to each other and to neurons is altered. This renders neurons more excitable and pain transmission is enhanced and prolonged."
Clinical note
Neuroinflammation produced by dysregulated immune cell activation more easily occurs in a biological 'terrain' in which immune tolerance has already been compromised (latent autoimmunity). The authors consider a combination of endomorphin-1, ultralow doses of naloxone and levetiracetam, but a number of other strategies emerge when case management includes comprehensively targeting the underlying causes of loss of immune tolerance and chronic inflammation. The role of dysregulated inflammation and immune dysfunction in any chronic pain condition should be borne in mind.The authors conclude:
"Surgery causes inflammation at the site of injury. Peripheral nerve injury can cause low-grade inflammation in the CNS known as neuroinflammation. Low-grade neuroinflammation can cause an imbalance in the glial–neuron interaction and communication. This renders neurons more excitable and pain transmission is enhanced and prolonged...Potentially, by targeting inflammatory activated glial cells and not only neurons, a new arena for development of pharmacological agents for persistent pain is opened."