Ischaemic Pain and Cold-induced Pain Experiment

Ischaemic Pain and Cold-induced Pain Experiment Results Ice water seems to bring about 60% more pain than tourniquet. Placebo was quite effective against tourniquet (91.7% ±4.33) and had no effect on ice water (100.7% ±2.74) which appeared to be the second strongest drug. Paracetamol 1000mg combined with 8mg of codeine had negative effect on tourniquet (105.9% ±7.91) as students sensed more pain after taking drugs, and slight effect on ice water (97.2% ±3.17) which made it become the weakest drug. Paracetamol 1000mg reduced the pain for tourniquet significantly (88.6% ±7.94) and also did well against ice water (95.2% ±3.55). Paracetamol 1000mg acted as the best drug for both tourniquet and ice water treatment. These results are shown in Figures 1 and 2 ( see Appendices for raw data and summary data).   Figure 1. Effects of drugs on mean pain response sensed from tourniquet and ice water. Mean pain units were measured for both tourniquet and ice water method for students. Students were then separated into groups A, B and C to take drug placebo, paracetamol 1000mg + Codeine 8mg and paracetamol 1000mg respectively. After 45 minutes the mean pain units were measured again for all of the students ( ± standard error, n=24). Figure 2 Effects of drugs on mean % pain control response sensed from tourniquet and ice water. Mean pain units were measured for both tourniquet and ice water method for students. Students were then separated into groups A, B and C to take drug placebo, paracetamol 1000mg + Codeine 8mg and paracetamol 1000mg respectively. After 45 minutes the mean pain units were measured again for all of the students . The pain levels after taking drugs were then divided by the pain units before taking drugs for each student to get the mean % control response ( ± standard error, n=24). Discussion Paracetamol is able to inhibit the cyclooxygenase (COX) and it is highly selective for Cytochrome c oxidase subunit II( COX-2) (Burkhard Hinz2008). Inhibition of COX enzymes causes the concentration of prostaglandin E2 to decrease, as a result, the hypothalamic set-point is lowered to reduce fever and the descending inhibitory serotonergic pathways is activated to produce analgesia (Anderson BJ 2008). Codeine is a pretty weak opioid analgesic. It has to be converted into morphine to function, this can be activated by the CYP2D6 metabolic. Codeine can reduce the analgesic efficacy in as the way it slow down the metabolizer of the drug(C. Mattia 2015). The combination of Paracetamol 1000mg with codeine 8mg is found to be more effective and safer than just using paracetamol or codeine (Aust Dent 2002). On the other hand, placebo would simply have no effect on pain level as it is just a sugar pill. As morphine inhibits hot and cold pain by inhibiting HPC but increases the firing of the cold cells, this leads to the burning sensation (Mogil 1999). This directly causes the paracetamol + codeine combination did not act what we thought, the burning sensation reduced the effectiveness of pain relief. As a result, for the ice water test, paracetamol worked as the best treatment and placebo was the weakest treatment. And for the tourniquet test which causes ischemic pain, muscle contraction increases hydrogen ions causes pH decreases and leads to acidosis, and infusion rate of acidic buffer increased and causes pain (Issberner 1996). However codeine and its product morphine are both hydrogen donors and would further increase the concentration of hydrogen inside muscle and causes more pain (Atkinson AP 2011). This explains why the paracetamol + codeine had negative effect on tourniquet test. The experiment result did not match up with hypothesis as paracetamol with codeine is not the most effective drug for both ice water and tourniquet tests. There are some steps for this experiment that can be improved. First of all at the beginning of the experiment, students cells were asleep and takes time to wake up and sense the pain correctly. Especially for ice water, as human skin would always get covered by a layer of oil secreted by sebaceous glands and dirt from environment mixture, the first attempt in ice water would take time to wash the layer off the skin and causes less pain sensed, after taking drugs, students arm were no longer protected and therefore would sense a stronger pain level faster, also the amount of ice in the tank was different and might causes error for the result. For tourniquet, students might not squeeze the rubble bulb correctly and causes difference between two runs. This experiment can be improved by getting a rubble bulb that squeeze itself automatically each time with same strength; maintain the ice water with same amount of ice and temperature; put arm into the ice water to wash off the layer and also wake it up before attempt the experiment, after five minutes of recovery (let the arm to warm up and get dried) then start the experiment. This experiment result can be used in clinical treatment and develop pain-relief drugs. In conclusion, the paracetamol 1000mg is the most effective drug to relieve both ischaemic pain and cold-induced pain. Appendices Table 1. Raw data collected and summary data for pain sensed before and after taking placebo. The mean, median, standard deviation (stdev), standard error of the mean (SEM) and n values calculated for pain units and % of pain changed before and after taking placebo.Mean pain units were measured for both tourniquet and ice water method for students. Student took placebo and after 45 minutes the mean pain units were measured again for all of the students . The pain levels after taking drugs were then divided by the pain units before taking drugs for each student to get the mean % control response ( n=24). Tourniquet 0 Tourniquet 45 Ice water 0 Ice water 45 Tourniquet % control Ice Water % Control 380 390 625 640 102.6 102.4 335 260 610 670 77.6 109.8 332 150 655 627 45.2 95.7 400 250 375 350 62.5 93.3 401 295 564 592 73.6 105.0 275 200 563 570 72.7 101.2 320 255 675 575 79.7 85.2 265 305 265 300 115.1 113.2 191 200 577 482 104.7 83.5 447 397 672 660 88.8 98.2 169 190 668 646 112.4 96.7 245 295 580 535 120.4 92.2 280 300 485 390 107.1 80.4 475 430 675 605 90.5 89.6 270 285 550 620 105.6 112.7 390 300 575 585 76.9 101.7 380 388 663 675 102.1 101.8 275 310 445 500 112.7 112.4 225 150 385 570 66.7 148.1 543 580 140 145 106.8 103.6 400 425 575 525 106.3 91.3 325 400 700 700 123.1 100.0 161 138 291 277 85.7 95.2 395 243 680 697 61.5 102.5 n 24 24 24 24 24 24 median 328.5 295 576 580 96.3 100.6 mean 328.29 297.33 541.38 539.00 91.7 100.7 stdev 96.97 106.14 150.86 146.49 21.2 13.4 SEM 19.79 21.67 30.79 29.90 4.33 2.74 Table 2. Raw data collected and summary data for pain sensed before and after taking paracetamol 1000mg + codeine 8mg. The mean, median, standard deviation (stdev), standard error of the mean (SEM) and n values calculated for pain units and % of pain changed before and after taking placebo.Mean pain units were measured for both tourniquet and ice water method for students. Student took paracetamol 1000mg + codeine 8mgand after 45 minutes the mean pain units were measured again for all of the students . The pain levels after taking drugs were then divided by the pain units before taking drugs for each student to get the mean % control response ( n=24). Tourniquet 0 Tourniquet 45 Ice water 0 Ice water 45 Tourniquet % control Ice Water % Control 380 340 630 625 89.5 99.2 533 538 471 525 100.9 111.5 225 320 550 565 142.2 102.7 350 275 597 585 78.6 98.0 345 150 647 675 43.5 104.3 575 260 645 520 45.2 80.6 175 300 425 530 171.4 124.7 249 234 353 299 94.0 84.7 280 160 600 520 57.1 86.7 255 163 648 615 63.9 94.9 263 250 660 665 95.1 100.8 260 280 355 340 107.7 95.8 200 375 440 420 187.5 95.5 185 160 540 325 86.5 60.2 435 368 600 595 84.6 99.2 345 315 535 435 91.3 81.3 315 265 472 575 84.1 121.8 220 300 575 600 136.4 104.3 450 545 565 683 121.1 120.9 235 418 476 523 177.9 109.9 125 160 595 555 128.0 93.3 277 370 670 660 133.6 98.5 60 63 511 500 105.0 97.8 460 540 565 378 117.4 66.9 n 24 24 24 24 24 24 median 270 290 565 542.5 98.0 98.2 mean 299.88 297.88 546.88 529.71 105.9 97.2 stdev 125.33 127.25 92.13 112.04 38.8 15.5 SEM 25.58 25.97 18.81 22.87 7.91 3.17 Table 3 Raw data collected and summary data for pain sensed before and after taking paracetamol 1000mg. The mean, median, standard deviation (stdev), standard error of the mean (SEM) and n values calculated for pain units and % of pain changed before and after taking placebo.Mean pain units were measured for both tourniquet and ice water method for students. Student took paracetamol 1000mgand after 45 minutes the mean pain units were measured again for all of the students . The pain levels after taking drugs were then divided by the pain units before taking drugs for each student to get the mean % control response ( n=24). Tourniquet 0 Tourniquet 45 Ice water 0 Ice water 45 Tourniquet % control Ice Water % Control 460 480 390 370 104.3 94.9 584 400 980 674 68.5 68.8 250 350 550 625 140.0 113.6 210 225 585 610 107.1 104.3 300 175 590 555 58.3 94.1 455 415 530 600 91.2 113.2 165 100 460 390 60.6 84.8 280 80 600 400 28.6 66.7 257 195 640 645 75.9 100.8 195 185 555 550 94.9 99.1 242 200 560 612 82.6 109.3 270 260 405 250 96.3 61.7 330 310 605 635 93.9 105.0 295 240 445 375 81.4 84.3 313 253 695 655 80.8 94.2 61 85 380 290 139.3 76.3 205 330 525 570 161.0 108.6 165 50 325 435 30.3 133.8 180 260 675 550 144.4 81.5 230 125 585 615 54.3 105.1 373 363 585 443 97.3 75.7 170 250 650 625 147.1 96.2 275 25 270 300 9.1 111.1 528 415 585 595 78.6 101.7 n 24 24 24 24 24 24 median 263.5 245 572.5 562.5 86.9 97.6 mean 283.04 240.46 548.75 515.38 88.6 95.2 stdev 123.24 125.39 143.93 131.49 38.9 17.4 SEM 25.16 25.60 29.38 26.84 7.94 3.55 References Anderson BJ. Paracetamol (acetaminophen): mechanisms of action. Pediatr Anesth 2008;18:915-21. Aust Dent J. 2002 Jun;47(2):147-51.Paracetamol versus paracetamol-codeine in the treatment of post-operative dental pain: a randomized, double-blind, prospective trial. Macleod AG1, Ashford B, Voltz M, Williams B, Cramond T, Gorta L, Simpson JM Burkhard Hinz,Olga Cheremina and Kay Brune, February 2008, The FASEB Journalvol. 22 no. 2 383-390 C. Mattia, F. Coluzzi, 2015,A look inside the association codeine-paracetamol: clinical pharmacology supports analgesic efficacy, Eur Rev Med Pharmacol Sci, Vol. 19 N. 3, Pages: 507-516. Oxford, 2007, league table of analgesic efficacy, viewed 13 May 2015, http://www.medicine.ox.ac.uk/bandolier/booth/painpag/acutrev/analgesics/leagtab.html. Issberner, Reeh and Steen (1996) Pain due to tissue acidosis: a mechanism for inflammatory and ischemic myalgia? Neuroscience Letters, Vol 208, 191-194. Mogil and Adhikari (1999) Hot and cold nociception are genetically correlated. The Journal of Neuroscience, Vol 19, RC25, 1-5.