Nociplastic Pain is relatively new concept among previously explained pain mechanisms. Previously there were two well known pain mechanisms that are nociceptive and neuropathic pains. Nociceptive pain usually caused by tissue damage while neuropathic pain are due to damage to the nervous system (PNS or CNS). Even though Nociplastic is a different pain type, it usually show mixed symptoms of other two pain patterns.
Since Physiotherapists play crucial role in controlling pain, the identification of pain origin is a necessary factor before choosing any pain management protocols.
Microglia And Pain
Microglia are specialized macrophage like cells in the CNS that help to maintain a homeostasis inside the brain by regulating the normal physiological conditions. Microglia have importance in managing and regulating the pain mechanism by process such as synaptic pruning, synaptogenesis and modifications. Peripheral nerve injury not only results in neuropathic pain, which is characterized by mechanical allodynia, a pain evoked by normally innocuous stimulation such as light touch, but also causes remarkable microgliosis in the spinal cord. Gliosis is a nonspecific reactive change of glial cells in response to injuries and insults and often involves the proliferation or hypertrophy of glial cells. Microgliosis manifests as profound morphological changes, where microglia transition from ramified to amoeboid shapes with enlarged cell bodies and shortened processes. Recent studies are focusing on controlling neural pain by controlling the neurogliosis process Microglia in the spinal cord horn are strongly activated after peripheral nerve injury. While C-fiber activation is sufficient to elicit spinal microglial activation, activation of large A-fibers is also important to maintain microglial activation. Multiple signaling molecules released from damaged primary afferents play a crucial role in the induction and development of spinal microgliosis. Peripheral nerve injury induces a rapid increase in the expression of colony stimulating factor 1 (CSF1) in injured DRG neurons. The CSF1 released from damaged primary afferents acts on spinal microglia to induce microgliosis and pain behaviors. Sensory neurons also release several chemokines after nerve injury to activate microglia. CCL2 is strongly upregulated in DRG neurons by nerve injury and contribute to neuropathic pain via CCR2 receptor. Neuronal proteases also play an important role in microglia activation. Nerve injury induces a rapid and transient upregulation of metalloproteinase-9 (MMP-9) expression in injured DRG neurons, which contributes to the induction but not maintenance of neuropathic pain.
Following peripheral nerve injury, in addition to morphological changes, spinal microglia begin to proliferate within 2 to 3 days and reach maximal levels in 4 to 7 days . Normally, microgliosis after nerve injury is a transient and self-limited event, and microglia return to normal levels within a few weeks. Nerve injury induced microgliosis is concomitant with the development of pain hypersensitivity. Accordingly, blocking microgliosis attenuates pain behaviors. It is important to point out that both spinal microgliosis and neuropathic pain development after nerve injury are age dependent and do not occur during the first several weeks of life due to the masking effect of anti-inflammatory cytokines such as IL-10.Microgliosis takes days to manifest after nerve injury. Thus, it was initially believed that microglia exclusively regulate chronic pain such as neuropathic pain with marked microgliosis but has no role in acute inflammatory pain conditions in which microgliosis is not as evident and robust.
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