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

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