BS 42025 The Psysiology And Pharmacology Of Pain

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BS 42025 The Psysiology And Pharmacology Of Pain

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BS 42025 The Psysiology And Pharmacology Of Pain

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Course Code: BS 42025
University: University Of Dundee

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Country: United Kingdom

Question:

How have animal models and mutations informed our understanding of nociception and possible new targets for analgesic drugs?
Nociception is the body’s response to harmful or potentially harmful stimuli, this response occurs via the sensory nervous system. This process is typically initiated by the stimulation of nociceptors by intense chemical, mechanical or thermal interactions such as touching something hot or injury such as cutting of the skin??

 
 
Answer:

Pain is a vital health concern for both humans and animals. To enhance the pain management and comprehend underlying mechanisms, pain animal models have been subsequently generated over the previous few years. This paper presents two novel models of acute pain produced for the evaluation of drug effects on the nociceptive reactions/responses in mice.  
The Transient Receptor Potential Cation Channel Vanilloid Subfamily V member 1 (TRPV1) remains a porous, non-selective cation conduit which is present in both neuronal like brain tissue and dorsal root ganglia alongside non-neuronal tissue like urinary bladder and skin. This TRP receptor acts an integrator of many noxious stimuli like heat, polyamines, anandamide, lipoxygenase products, acid and capsaicin. It opens in reaction/response to noxious chemical and thermal stimuli. The activity of TRPVI is modulated by inflammatory mediators. The nociceptive responses are reversed by many TRPVI antagonists in rodents with inflammatory status.
The first model will be helpful in the determination of MAC sparing effects on the agent in the course of the noxious emotional stimulus of both ovary and ovarian ligaments in anesthetized mouse. This strategy or technique was designed for mice and subsequently modified to probe the anesthetic sparing effect of various drugs in mice. The 2nd model will be helpful in the evaluation of efficacy analgesic medications in a conscious mouse utilizing nociceptive threshold testing devices (Minett et al. 2015).
The use of thermal and mechanical nociceptive threshold testing device has been used in the evaluation of anti-nociceptive effects array if drugs like buprenorphine in mice. These models have been useful in our understanding of nociception and possible new targets for analgesic drugs (Simmons 2008). This is because they are both promising to test analgesic effects of a range of drugs efficiently. During the ovary and ovarian ligament simulation in mice, the maropitant, the NK-1 antagonist has significantly reduced the requirements for anesthetic.
This helps indicate that maropitant might have anti-nociceptive features thereby encouraging as well as bolstering further probe of this agent in the clinical trials. The orotransmucosal buprenorphine has also surged mechanical and thermal nociceptive threshold in mice utilizing the three testing devices (Liedtke 2006). These discoveries show the potential of OTM route as the best alternative administration of buprenorphine for treatment of pain in mice.   
Over the past few decades, our understanding of the fundamental pain physiology has surged broadly. This is due to the use of an animal model that is an essential constituent of this progress. It stays crucial for the comprehension of pain mechanism and new pharmacological targets identification in pain therapy. It is also useful in enhancing treatment of pain and finding analgesic drugs clinical dosing (Rowe, Xiao, Rowe, Cummins, and Zakon 2013). The initial investigative energies were directed to an animal model of acute as well as nociceptive pain evaluation of effects of physiological pain on the healthy tissue through the application of a quantifiable noxious stimulus to the animal till a response/reaction is triggered.
Consequently, the pain models have sought efficiently to explore pathological pain mechanism emerging from both inflammation and neuropathic pain besides that triggered by illness. The use of nociceptive physiological and behavioral responses noxious stimulation as indirect pain indicators have improved the understanding of nociception and possible new targets for analgesic drugs. This is because it has eliminated the critical problem of pain assays whereby pain itself remains extraordinarily subjective and individualized hence hard to assess, particularly with the non-verbal subjects.
The pain assessment model and mutations or assessment tools in animal models have efficiently helped assess the behavior hence boosting our understanding of nociception and possible new targets for analgesic drugs. Two primary devices that have enhanced this understanding through increased efficiency in pain identification include analgesiometers and pain scaling systems (Gregory et al. 2013). These tools are accurate and validated techniques thereby facilitating efficient management approaches to pain.
 
 
Pain Scaling Systems: These systems have been essential in studying both clinical and preclinical pain. The modification of human pain scales to develop animal in 1978 by LaMotte and Campbell was the turning point towards a useful understanding of nociception and possible new targets for analgesic drugs. This is because they compared the nociceptive responses to thermal stimulation intensity in monkeys with the scale utilized on human being thereby efficiently assessing responses to the thermally induced pain.
The model was also used by Taylor and Houlton in the year 1984 to probe the postoperative analgesic effect of buprenorphine, morphine, alongside pentazocine in mice after orthopedic surgery employing numerical rating scale (NRS) together with Simple Descriptive Scale (SDS). Similarly, Visual Analogue Scale (VAS) was applied in comparing postoperative analgesic effect between medications for pain in mice. The three scales NRS, VAS, and SDS, have helped rate pain by intensity.
Analgesiometers is an objective instrument for pain research. These devices (analgesiometry) have been established thereby generating quantifiable noxious stimulus (mechanical, thermal, chemical, and electrical) of measuring nociceptive thresholds. Subsequently, four categories of models have been developed including acute, neuropathic, inflammatory and clinical-based pain models.
Acute Pain Model has permitted the investigators to comprehends pain mechanisms and efficiently evaluate pain medications analgesic efficacy in healthy animals. Both voluntary and reflexive behaviors responding to the noxious stimulus are used commonly as pain indicators. Somatic pain testing of this model uses tail-flick and hot plate tests whereas visceral pain testing asses nociceptive responses in viscera.
Inflammatory Pain Model induces a painful condition which mimics clinical inflammatory pain which is a considerable health concern triggering suffering in many animals. This model has surged the understanding of scientist with regards to underlying inflammatory pain mechanisms and subsequently develop potential treatments that keep pace with mutations. It uses Von Frey filaments as emblematic mechanical nociceptive threshold testing. This technique is useful as it detects mechanical allodynia in the inflammatory and neuropathic pain model (Dunn, Cannon, Irwin and Pinkert 2012).
Animal pain models have proven crucial in pain studies. Research provides fundamental comprehension of mechanisms of pain and enhances the treatment of pain thereby informing our understanding of nociception and possible new targets for analgesic drugs. Many animal pain models have been designed to display clinical pain, and when the experimental condition is favorable hence no interfering with test results, our understanding of nociception and possible new targets for analgesic drugs can significantly improve.
The pain clinical trials using these model have helped evaluate the potential drugs’ analgesic efficacy that demonstrated promising outcomes previously in the lab animals’ models. Such testing drug is administered to clinical patients, and they trial unearth how clinical pain condition reacts/responds to treatment as well as determine the drug side effects (Diochot et al. 2012). Clinical trials through these models translate information from lab experiments directly into clinical use. The outcomes from clinical trials are, therefore, valuable in enhancing our understanding of nociception and possible new targets for analgesic drugs.
 
 
References
Diochot, S., Baron, A., Salinas, M., Douguet, D., Scarzello, S., Dabert-Gay, A.S., Debayle, D., Friend, V., Alloui, A., Lazdunski, M. and Lingueglia, E., 2012. Black mamba venom peptides target acid-sensing ion channels to abolish pain. Nature, 490(7421), p.552.
Dunn, D.A., Cannon, M.V., Irwin, M.H. and Pinkert, C.A., 2012. Animal models of human mitochondrial DNA mutations. Biochimica et Biophysica Acta (BBA)-General Subjects, 1820(5), pp.601-607.
Gregory, N.S., Harris, A.L., Robinson, C.R., Dougherty, P.M., Fuchs, P.N. and Sluka, K.A., 2013. An overview of animal models of pain: disease models and outcome measures. The Journal of Pain, 14(11), pp.1255-1269.
Liedtke, W.B. ed., 2006. TRP ion channel function in sensory transduction and cellular signaling cascades. CRC Press.
Minett, M.S., Pereira, V., Sikandar, S., Matsuyama, A., Lolignier, S., Kanellopoulos, A.H., Mancini, F., Iannetti, G.D., Bogdanov, Y.D., Santana-Varela, S. and Millet, Q., 2015. Endogenous opioids contribute to insensitivity to pain in humans and mice lacking sodium channel Na v 1.7. Nature communications, 6, p.8967.
Rowe, A.H., Xiao, Y., Rowe, M.P., Cummins, T.R. and Zakon, H.H., 2013. Voltage-gated sodium channel in grasshopper mice defends against bark scorpion toxin. Science, 342(6157), pp.441-446.
Simmons, D., 2008. The use of animal models in studying genetic disease: transgenesis and induced mutation. Nature education, 1(1), p.70.

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