Central sensitization is an amplification of neural signaling within the central nervous system that elicits pain hypersensitivity. (Woolf, 2011). It is a pathological phenomenon that represents both structural and functional changes in the CNS and leads to increased responsiveness of nociceptive pathways which will result in pain hypersensitivity. This plasticity of the somatosensory nervous system comprises neurobiological changes in the dorsal horn neurons such as increased excitability, strengthened synaptic transmission, and decreased inhibition.
Many factors are known to predispose patients to the development of CS, and these might include gender (females), dysfunction of the neuroendocrine and/ or the autonomic system, physical trauma, and emotional stress. Abnormal regulation and output of the hypothalamic-pituitary-adrenal (HPA) axis is commonly associated with centralized pain disorders. The HPA axis is the primary stress response system and its activation results in downstream production of cortisol and a dampening of the immune response. (Eller-Smith et.al, 2018).
Centralized pain often occurs in patients who have fibromyalgia Syndrome (FMS), chronic fatigue syndrome (CFS), migraine, irritable bowel syndrome (IBS), temporomandibular disorders (TMD), and it also presents following neurological injuries such as a stroke or a spinal cord injury. FMS is a pain-amplification syndrome. Persons with FMS have increased sensitivity to painful and nonpainful stimuli, including touch, heat, cold, light, sound, and smell. (Henry et.al, 2011).
1. Pain characters: The pain is usually lasting for more than 3 months for no apparent reason. Because central sensitization results from changes in the properties of neurons in the central nervous system, the pain is no longer coupled, as acute nociceptive pain is, to the presence, intensity, or duration of noxious peripheral stimuli. Instead, central sensitization produces pain hypersensitivity by changing the sensory response elicited by normal inputs, including those that usually evoke innocuous sensations. (Latremoliere et.al, 2009).
Chronic pain is manifest in a variety of ways, including spontaneous pain; enhanced sensitivity to painful stimuli (hyperalgesia); pain in response to normally innocuous stimuli, e.g., gentle brushing of skin (mechanical allodynia) or mild cool temperatures (cold allodynia); and aberrant referral of pain to unaffected body parts. (Kuner et al, 2020).
2. Comorbidities: Generalized fatigue, sleep disturbances, poor quality of life, and mood disorders (anxiety, depression, panic disorders, and pain catastrophizing).
Centrally-acting drugs need to be used in CS pain management: TCAs, SNRIs, SSRIs, pregabalin, gabapentin, and tramadol. It should be remembered that these drugs may also have a significant supraspinal mechanism of action, in particular, antidepressants, which may act on the significant psychological component of pain perception and thus allow patients to better cope with their pain. (Nijs et.al, 2014). Due to both the complexity of CS and the heterogenicity in the responsiveness to a certain drug over the other among CS patients, it is usually a good idea to use a cocktail of these medications to target the different mechanisms involved in CS pain. A major disadvantage of pharmacological treatment is the serious side effects associated with it.
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