Almost everyone feels Pain from time to time. When you cut your finger or feel a tug, Pain is how your body can tell that something is wrong.
When an injury activates pain sensors, they send a message in an electrical signal, which travels from one nerve to another until it reaches the brain. The brain processes the signal and sends the message that you are hurt.
The signal usually stops when the cause of the Pain is resolved.
Chronic Pain is different. Your body hurts weeks, months, or even years after the injury. In this case, the nerve signals continue to be activated even after the wound has healed.
The mechanisms behind chronic Pain remain unclear even to scientists. Although, today, it is known that a type of accessory cells of neurons – glial cells – are responsible for contributing to this process.
Glial cells, metabolism, and chronic Pain
The schematization of the process of chronic pain product of an injury. Functional and structural changes in glial cells, mitochondrial dysfunction, and neuroinflammation (in the celestial release of cytokines) and its subsequent chronification of Pain in the central nervous system even when the damage has been solved.
Until recently, glial cells were thought to have a purely supportive function for neurons, providing physical and nutritional support. However, today, it has become clear that glial cells are active and involved in various neurological processes, including chronic pain.
Glial cells are not neural in origin but neuroimmune cells with different phenotypes. In the CNS, they are classified as astrocytes, oligodendrocytes, and microglia, with astrocytes being the most abundant.
In chronic pain situations, changes occur in the function, activity, and structure of glial cells. One of the hallmarks of neuroinflammation is an increase in the energy metabolism of the glia.
These changes lead to neuronal dysfunction and consequent neuronal death that has been observed in chronic neurodegenerative diseases.
Mechanisms of Chronic Pain
The mechanisms behind chronic Pain are not yet apparent; its multi-causality is closely related to the activation and communication of neurons and glia, two cell types present in our nervous system.
What is known today? For Pain to become chronic, two neuronal processes must occur sensitization in the peripheral area and sensitization in the CNS.
Sensitization in the peripheral area occurs in an environment with different actors capable of causing damage to the microglia. Under these conditions, astrocytes begin to mediate cytokines, and glial cells respond with the mechanism known as glial activity.
By becoming reactive, glial cells change metabolism and activate synaptic contacts that enhance SCN sensitization. If this is maintained for a sufficient period, chronic pain can appear.
DCA: a solution for chronic Pain?
Noting changes in the mitochondrial function of the spinal cord in models of chronic neuropathic and persistent inflammatory Pain, they decided to study the effect of dichloroacetate (DCA, an inhibitor of a mitochondrial enzyme: pyruvate dehydrogenase kinase) as a potential treatment for chronic pain.
A condition that today does not have effective pharmacological therapies. They observed that oral administration of DCA in the short term after injury improves mitochondrial bioenergetic parameters, glial reactivity in the spinal cord is reduced, and most importantly, it may be effective in improving behavior in two chronic pain models.
Increased spontaneous or provoked pain sensitivity and pain sensation to stimuli that generally do not produce Pain, termed respectively hyperalgesia and allodynia.
In highly controlled doses, DCA is a controversial drug that has obtained positive clinical responses to treat some types of cancer. However, its use for human treatment is not yet recommended. The fact that it is already being used in the clinic makes therapy with promising results, although its efficacy is still being exhaustively studied.
Glial cell metabolism is closely related to the mechanisms of chronic pain generation.
There are no efficient therapies to alleviate chronic pain since it is a multicausal disease that makes it difficult to mitigate. Attacking these metabolic pathways with drugs is one of the strategies proposed by scientists.