systems are involved (‘neuroinflammation’), playing a significant role in the pathogenesis of acute and chronic pain as well as chronic neurodegenerative diseases and neuropsychiatric illness. Neutrophils are usually the first respondents of an inflammatory response and gather at the site of injury via the bloodstream, followed by the release of other chemical mediators. Inflammation may lead to three major responses: hyperalgesia, allodynia, and sympathetic maintained pain. Inflammation can also induce mast cell degranulation, which subsequently leads to the release of platelet-activating factor (PAF) and stimulates the release of 5-HT from the circulating platelet (Piancone et al., 2021). The cardinal signs of inflammation include the hot inflamed site due to an increase in blood flow toward the region, redness, and swelling due to vascular permeability pain caused by the activation and sensitization of primary afferent neurons and lasting loss of function. The localized inflammatory response then induces the release of free arachidonic acid (AA) from the phospholipids, which are converted into prostaglandins (PG) via the cyclooxygenase (COX) pathways. Peripheral neuroinflammatory pain Acute peripheral inflammation occurs after injury and/or infection, and it may be associated with acute inflammatory pain. After tissue damage, local macrophages release mediators that result in the so-called inflammatory response. Inflammatory mediators acidify the tissue, which activates nociceptive primary afferent neurons and lowers their signaling thresholds. These conditions increase the sensation of pain, both peripherally and centrally. Both peripheral and central mechanisms have been identified as contributing to endogenous analgesia during inflammation. These endogenous analgesic compounds Neurogenic pain/inflammation Neurogenic inflammation describes the inflammatory response observed following the release of proinflammatory mediators from peripheral terminals of activated primary (afferent) sensory neurons. Mechano-insensitive, but heat- and chemo- sensitive, C nociceptors are responsible for the neurogenic vasodilation in human skin. These sensory receptors ending in the dorsal horn of the spinal cord release neurotransmitters and neuromodulators in response to peripheral noxious stimuli. As a result of local depolarization, the nociceptive sensory neurons release proinflammatory mediators in the periphery, which produce vasodilatation and edema. They can recruit and activate immune cells as well as adaptive immune cells, which, together with the mediators released from the immune cells, participate in the phenomenon of neurogenic inflammation. Calcitonin gene-related peptides, substance P, and several other neuropeptides are the main mediators responsible for the sequence of pathogenic events leading to neurogenic inflammation (Mangus et al., 2022). The stimuli influencing neurogenic inflammation activate the transient Case study 3 Zain started a career life earlier than an average Canadian living in Calgary. At just 25 years of age, he competed in and won three different national championship slams in Rugby. In every state of the country, his story—much too high levels of commendations—is shared proudly in different youth boot camps of nearly every sports scouting event. The ‘Headbull,’ as he is proudly called, Zain had gained national prominence after signing for the Fluminense Rugby Team as an up-field attacker in 2013. With the demand of his role of play, he is expected to make aggressive over-the-top runs at a charging barrage of opponent lines. He is well known for his signature ‘bull-them-all’ runs executed as a daring charge through the opponent lines using the head and an overly flexed shoulder positioning. Not only has this move gained him prominence in the National Rugby League, but it has also won him numerous ‘Player of the Match’ and ‘Player of the Tournament” awards. Safe to say, Zain enjoyed an early rugby career in glitz, fame, and glamour.
Pain from inflammation can be further classified into two types: chronic and acute pain. Acute inflammatory pain is normally intense and occurs for a brief period, which is initiated as a response to harmful stimuli that are normally mediated by the Aδ-fibers. Leukocytes and plasma from the bloodstream are accumulated at the site of the injury to assist in the inflammatory process. However, prolonged inflammation, better known as chronic inflammatory pain , lasts beyond the expected period of healing, which is typically mediated by C-fibers. There is a progressive shift of mononuclear cells at the site of the inflammation as well. Inflammatory pain causes the increase of afferent input into the DH of the spinal cord and leads to the development of central sensitization (Ustianowska et al., 2022). There are some mediators produced at the site of injured tissue, which include 5-HT, kinins, histamine, nerve growth factors (NGF), adenosine triphosphate (ATP), PG, glutamate, leukotrienes, nitric oxide (NO), NE, and protons. include opioid peptides, endocannabinoids, somatostatin, and anti-inflammatory cytokines. The activation of peripheral nociceptive C and Aδ fibers of primary afferent neurons, by several proinflammatory mediators such as histamine, serotonin, H+, and cytokines, gives rise to action potentials that are conducted to the dorsal horn of the spinal cord (Castroman et al., 2022). Subsequently, through several neuronal pathways, the nociceptive information can reach the higher brain centers, including the thalamus and cortex. receptor potential (TRP) ion channels and the purinergic (P2X) receptors, which play a crucial role in the development of inflammation and the perception of pain. Therefore, ligands to these receptors or drugs able to counteract proinflammatory molecules may represent promising avenues in the management of inflammatory pain. Recent evidence suggests that triggering the combined actions of neurons and immune/vascular cells in the central nervous system (CNS) may be associated with neuronal activity, exhibiting a profile similar to other neuroinflammatory states. The term “neurogenic neuroinflammation” was then proposed to define inflammatory responses triggered by neuronal activity in the CNS. It was postulated that neurogenic neuroinflammation might have useful effects associated with regeneration processes (Manchikanti et al., 2020). In this context, maladaptive responses may arise when neurogenic neuroinflammation persists or spreads, becoming markedly relevant in conditions such as pain or epilepsy. However, this would not last forever, at least not for the length of his playing career that abruptly ended in 2018—5 years after his debut as a senior rugby player. Zain’s injury woes all started in June 2017, when Zain was stretchered off the field of play for a tackle he received from an opposition defender. Although cleanly executed, the tackle appeared to have immobilized Zain. He had groaned in pain and immediately complained about a ‘painful tingling sensation running through the neck to the back.’ First aid assistance on the field could not help, and he was stretchered off for special medical care. He would return to open play 4 months later after missing 10 championship games. However, his posture had changed, he made fewer executions of his signature run, and most importantly he changed from an up-field attacking role to a wide-receiver role.
Book Code: PYFL4024
Page 136
EliteLearning.com/Psychology
Powered by FlippingBook