The Essay On Nociceptive Pain Mechanism And Opioid Drug Use For Pain Management.

Nociception and its neural processes

The concept pain and nociception are not same rather it can be stated that the nociception is basically a subcategory of the somatosensation. The nociception mainly refers to the neural processes of coding and processing of the noxious stimuli. When the signal arrives at the central nervous system due to the stimulation of specific sensory receptors present in the peripheral nervous system named nociceptor, then the signal is named as nociception (Coghill, 2020). The activation of the nociceptors takes place due to the presence of the noxious stimuli and the process of nociception is basically the physiological process of protecting the body from any type of damage. The nociceptors can be activated by three types of stimuli that is mechanical stimuli, temperature and the chemical stimuli. The pain arises due to the activation of the nociceptors is mainly known as the nociceptor pain. Nociceptors are generally present in the different free nerve endings and it is reported that the nociceptors are mainly present in the regions like visceral pleura, articular cartilage, brain, pericardium, lung parenchyma, and cord tissue. For managing the nociceptive pain conditions among the patients, the use of the opioids is very common (Bell, 2018).

In this essay, the mechanism of nociceptive pain and the use of opioid drugs for managing the pain conditions are depicted in brief.

The pain sensation can travel through nociceptive pathway by mainly three manner and there are two types of fibres including the Aδ fibre and the C fibre. In case of the Aδ fibre there are two different subtypes- Type I and Type II. The type I fibres are mechanically sensitive in nature along with having strong sensation towards the heat and chemical stimuli. On the other hand, the type II fibres are more sensitive to the higher mechanical thresholds and this type of fibres are mainly accountable for the mediation of the acute pain. The type C fibres are mainly accountable for the carrying the dull pain sensation or the slow pain (Klinck & Troncy, 2016). The pain sensation is mainly carried out by the activation of the ion channel present on the nociceptors. For example, the proton activation process of acid-sensing ion channels (ASIC) can be mentioned and the process of the cation influx depolarises potential of the nociceptor producing receptor. In case, the potential of receptor is not adequate to reach the activation potential threshold of the voltage-gated Na⁺ channels (NaV), it will activate initiation process of action potential and eventually a transmission of a signal to the spinal cord will occur to generate the pain condition as well (Yang & Lai, 2021).

While discussing about the specific mechanism of the nociceptive pain pathway in case of the human beings, it can be reported that the nociceptors are mainly associated with the hyperalgesia that is the increased pain sensation and the feeling of pain due to the damage to the nerves or alteration of the chemicals associated with the nerve pathways responsible for sensing the pain in the body (Sandström et al., 2019). The nociceptors not only carry the afferent information to the dorsal horn of the spinal cord when they are activated, but they also start the process of neurogenic inflammation. Neurogenic inflammation results in the release of neurotransmitters such as substance P and calcitonin gene-related peptide (CGRP), resulting in severe dilatation and plasma leaking of proteins and fluid from post capillary venules (Ramachandran, 2018). The impulses can enter peripheral arborizations innervating other areas in the afferent's receptive field (axon reflex) and it causes peptides like CGRP, somatostatin, substance P and other bioactive ingredients such as cytokines to release from the terminal into the interstitial tissue. The released chemicals have a variety of paracrine and autocrine actions on epithelial, endothelial, and resident immune cells (Langerhans), resulting in arteriolar vasodilation (flare) and/or enhanced vascular permeability and plasma extravasation from venules (oedema, via substance P) (Kee, Kodji, & Brain, 2018). The build-up of neurogenic inflammation along with inflammatory mediators is aided by released enzymes (e.g., kallikreins) and blood cells (e.g., platelets, mast cells). Non-neuronal cells (e.g., neutrophils, monocytes, mast cells, fibroblasts, and platelets), along with the sensory endings of primary afferent fibres, emit a variety of substances that mediate or facilitate the inflammatory process. Prostaglandins, thromboxanes, platelet-activating factor, serotonin, histamine, protons, leukotrienes, bradykinin, SP, purines including adenosine and ATP, and free radicals are all inflammatory mediators (Ringkamp, Dougherty & Raja, 2019). During inflammation, cytokines like interleukins and tumour necrosis factor, as well as neurotrophins like NGF, are produced. In this regard, it is essential to consider the fact that the bradykinins and the prostaglandins are not associated directly with the nociceptive pain rather they are responsible for increasing the pain sensation and also increase other endogenous chemicals by increasing the frequency of action potential firings in response to the natural stimuli (St John Smith, 2018).

Types of fibres involved in pain sensation

The utilization of the opioid for the management of the nociceptive pain is very common and there are different drugs that are used for managing the pain condition.

Opioid under the name of oxycodone is used for management of the moderate to severe level of pain sensation. The proprietary name of this particular drug is Oxycontin and the generic name of the drug is oxycodone hydrochloride. Considering the chemical composition of the drug reveals that the drug has the chemical name of 4, 5α-epoxy-14-hydroxy-3-methoxy-17-methylmorphinan-6-one hydrochloride (C₁₈H₂₁NO₄) (Drugbank.com, 2022).

The drug exerts its action straight on different types of tissues which are even not associated to its pain-relieving effect. The tissues are mainly the tissue include the respiratory centre in the brain stem, the cough centre located medulla of brain, gastrointestinal tract, muscles of the pupils, endocrine system, immune system and cardiovascular system. The exact mechanism of action of oxycodone is unidentified.  The receptors that has active binding sites for opioids are present in the gastrointestinal tract, liver, heart, lungs, and reproductive system are increased and delivered to nerve terminals during inflammation or hyperalgesia (Kinnunen et al., 2019). Opioid agonists include oxycodone and its vigorous metabolites, noroxymorphone, noroxycodone and oxymorphone are responsible for managing the condition. These chemicals may passively diffuse or be actively transferred through the blood-brain barrier by an unknown method. The mu opioid receptor located in the CNS or central nervous system have the binding sites for oxycodone and its active components and peripheral nerves, as well as the kappa and delta opioid receptors, and activate a G protein coupled receptor dependent signalling pathway.  Mu opioid receptor activation suppresses N-type voltage-operated calcium channels, which diminishes the sensation of pain (Umukoro et al., 2021).

While discussing the pharmacokinetics of the drug, it can be reported that the drug has the oral bioavailability of 60 per cent to 87 per cent and this is not at all affected by the consumption of food. The maximum plasma concentration of the drug is 11.5ng/ml and the time to maximum concentration is 5.11hr among the patients who have given patients an oral immediate release dose of oxycodone (10mg). In case metabolism of the drug, it can be reported that the hepatic metabolism of the drug is extensive in nature and it is completed through four main reactions. The 3A5 and CYP3A4 are responsible for performing N-demethylation, CYP2D6 is associated with O-demethylation and on the other hand, unknown enzymes perform 6-keto-reduction followed by conjugation (Drugbank.com, 2022).

The drug can be delivered through oral, subcutaneously, intramuscularly, intravenously and rectally as well.

Indications, contraindications, precautions and side effects

The drug can be used during moderate to severe level of pain sensation and extended-release medicines can be used to treat the chronic pain conditions as well. As a part of the contradictions of the drug, it can be reported that the drug should be avoided in case of delayed gastric emptying, acute abdomen, cor pulmonale, severe chronic obstructive lung disease, paralytic ileus and severe bronchial asthma. The side effects of the drug include the stomach pain, headache, flushing, mood changes and the dry mouth. As a part of the precautions of the drug, it can be reported that during pregnancy the drug should be avoided to prevent the respiratory depression among the neonates (Drugbank.com, 2022).

Activation of nociceptors and pain generation

It is crucial for the nurses and the health care professionals to have adequate knowledge regarding the use of the medicines including the side effects and contradictions of the drug. In this regard, it can be reported that, the proper knowledge regarding the side effects and the precautions about the drug administration will allow the nurses to use the drug properly in the severe and moderate level of pain and thus identification of the proper adverse effects associated with the drug will allow the nurses to take the required actions for managing the adverse drug reactions. Moreover, the nurse’s knowledge about the drug reactions can also help them to aware the patients and their families about the conditions which will eventually enhance the satisfaction of the patients and the family members (Hammar et al., 2021).

Conclusion

From the above analysis, it can be reported that the nociceptive can be managed by using the opioids. In this regard, the use of Oxycontin can be recommended and the generic name of the drug is oxycodone hydrochloride. The activation of the nociceptors takes place due to the presence of the noxious stimuli and the process of nociception is basically the physiological process of protecting the body from any type of damage.  The nociceptors can be activated by three types of stimuli that is mechanical stimuli, temperature and the chemical stimuli. The pain arises due to the activation of the nociceptors is mainly known as the nociceptor pain. The side effects of the drug include the stomach pain, headache, flushing, mood changes and the dry mouth. The knowledge about the drug and the nociceptive pain can help the patients and their family members to avoid the possible adverse effects.

References

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Drugbank.com (2022). Oxycodone. Drugbank.com. https://go.drugbank.com/drugs/DB00497

Hammar, T., Hamqvist, S., Zetterholm, M., Jokela, P., & Ferati, M. (2021). Current Knowledge about Providing Drug–Drug Interaction Services for Patients—A Scoping Review. Pharmacy, 9(2), 69. https://www.mdpi.com/1047152  

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Klinck, M. P., & Troncy, E. (2016). The physiology and pathophysiology of pain. In BSAVA manual of canine and feline anaesthesia and analgesia (pp. 97-112). BSAVA Library. https://www.bsavalibrary.com/content/chapter/10.22233/9781910443231.chap8 

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Ringkamp, M., Dougherty, P. M., & Raja, S. N. (2018). Anatomy and physiology of the pain signaling process. In Essentials of pain medicine (pp. 3-10). Elsevier. https://www.sciencedirect.com/science/article/pii/B9780323401968000012 

Sandström, A., Ellerbrock, I., Jensen, K. B., Martinsen, S., Altawil, R., Hakeberg, P., ... & Kosek, E. (2019). Altered cerebral pain processing of noxious stimuli from inflamed joints in rheumatoid arthritis: An event-related fMRI study. Brain, behavior, and immunity, 81, 272-279. https://www.sciencedirect.com/science/article/pii/S088915911831211X 

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