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IOSR Journal of Pharmacy
e-ISSN: 2250-3013, p-ISSN: 2319-4219, www.iosrphr.org
Volume 2 Issue 6 ‖‖ Nov-Dec. 2012 ‖‖ PP.01-04

   Sex related difference in response to experimental pain in first
                        year medical students
                   Samir Mendpara1 Veena Jasuja2 Geetanjali Purohit3
                              BM Palan4 JM Harsoda5
                           1
                           Dr.Samir Mendpara (Resident doctor in Physiology)
                                  2
                                    Dr. Veena Jasuja (Tutor in Physiology)
                              3
                                Ms. Geetanjali Purohit: (Tutor in Physiology)
                           4
                             Dr. BM Palan: (Associate Professor in Physiology)
                              5
                                Dr.JM Harsoda: (Prof & Head in Physiology)
                         SBKS MI & RC, Sumandeep Vidyapeeth, Vadodara, Gujarat


Abstract––Pain is complex multidimensional experience influenced by physical, psychological, and social
factors. In recent years sex differences in responses to pain have received increased attention. Purpose of
study was to determine sex differences in experimental pain response. For this study cold pressor test was
used to exert experimental pain. 100 medical students (50 boys and 50 girls) participated in study. Subject
was asked to submit his hand into container with ice water. Radial pulse was measured before and
immediately after test to determine pulse reactivity. Pain threshold and tolerance were measured. Subject was
asked to determine intensity of pain during test and rate on VAS. Data was statistically analysed using
student t-test and Correlation Coefficient. Pain threshold and pain tolerance were significantly more in boys,
Pain rating was significantly more in girls. Pain reactivity was significantly more in girls. In both sexes,
baseline pulse showed positive relationship with pain threshold and pain tolerance and negative relationship
with pain rating. Women typically displaying greater pain sensitivity than men, but mechanisms underlying
differences remain unclear. Possible explanation suggests that men are more motivated to tolerate and
suppress expressions of pain because masculine sex role, whereas feminine sex role encourages pain
expression. Different pain perception might account for sex difference in pulse reactivity. Hormonal
influences may play minor role.

                                         I.       INTRODUCTION
          Pain is the main reason for visiting the emergency department in more than 50% of cases and is present
in 30% of family practice visits. Several epidemiological studies from different countries have reported widely
varying prevalence rates for chronic pain, ranging from 12-80% of the population (1).
          The International Association for the Study of Pain's widely used definition states: "Pain is an
unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in
terms of such damage" (2).
Pain is a complex multidimensional experience influenced by physical, psychological, and social factors. In
recent years sex differences in responses to pain have received increased attention. Multiple studies have
investigated sex differences in experimental pain perception using a wide variety of noxious stimuli (3).
          For this study, the cold pressor test was used to exert experimental pain. The cold pressor test (CPT) is
an empirically validated test commonly used in research on stress, pain and cardiovascular reactivity. George E.
Brown and Edgar A. Hines in 1932 introduced a test designed to detect latent states of hypertension by
immersion of one extremity in ice water for 1-3 minutes. This test was called as Hines and Brown test. Later
on name of this test was changed to cold pressor test. Cold pressure test is simple, provocative, non-invasive,
reliable and cheap test to know autonomic status of body (4).
          If variation in response to experimental pain according to age, sex, race etc, is studied, it is quite
possible that more effective analgesia could be developed on the basis of these differences.

                                       II.     AIM AND OBJECTIVE
        The purpose of this study was to determine sex differences in experimental pain response. For this
study pain threshold, pain tolerance and pain rating as three pain sensitivity parameters and radial pulse as
cardiovascular parameter were selected to study the response of experimental pain.

                                                        1
Sex related difference in response to experimental pain in first year medical students

                                     III.    MATERIALS & METHODS
         Total 100 young volunteers, medical students of S.B.K.S. medical college and research centre
participated as subject in this study. 100 students were taken in two groups. First was group of 50 male students
and second was group of 50 female students. The present study was conducted in clinical laboratory,
Department of Physiology, S.B.K.S. medical college. Written informed consent was obtained according to
ethical committee policy. On the day of testing, the subject signed an consent form acknowledging their
willingness to participate in the study. Before testing, every subject was interviewed for recent history and
examined for respiratory disease and cardio-vascular disease and subjects with such type of diseases were
excluded from the study. Person taking analgesic for pain relief was excluded from the study.

        Subjects were asked to sit comfortably in chairs. After rest for around 10 minutes, resting radial pulse
was counted for one minute and recorded as rate per minute. Laboratory water bath was filled with ice cold
water and temperature of cold water was measured using laboratory thermometer. Temperature of cold water
was maintained between 4˚ C to 8˚ C by adding required ice cold water to the container (5).

         After that, subject was asked to submit his/her dominant hand into a container with ice water (palm
down, up to 5 cm above wrist level). Immediately, two stop watches were started. Subject was asked to
determine intensity of pain during test and rate it on a scale of 0 to 10 and for that subject was explained that
Zero represents no pain at all while 10 represents the worst imaginable pain (6). Subject was explained that once
pain was present during test, they let the researcher know. One stop watch was stopped. This provided pain
threshold (first feeling pain). Once the pain was unbearable, the participant removed his/her hand, second stop
watch was stopped and this provided pain tolerance. Immediately after test radial pulse rate per minute was
measured.

Statistical analysis: Data was collected and statistical analysed using student t test and zero order correlation
coefficient.
                               IV.          OBSERVATION AND RESULTS
                       Table 1: Difference in various parameters between male and female.
          Parameters            Male                    Female                T value       P value
          Pulse (rate/min)      78.94 ± 7.05            77.58 ± 7.54          0.98          0.35
          Pulse reactivity      7.0 ± 6.25              12.58 ± 7.86          3.92          0.0001**
          PTh (sec)             22.72 ± 8.96            17.68 ± 6.59          3.2           0.001**
          PTo (sec)             66.92 ± 22.32           50.98 ± 15.40         4.15          0.043*
          PR (VAS)              6.0 ± 0.83              6.58 ± 0.90           3.33          0.001**
Data is demonstrated in MEAN ± SD. unpaired t-test, df : 98
* Difference significant at p<0.05 ** Difference highly significant at p<0.01
Pulse reactivity = after CPT pulse – Baseline pulse.
PTh: pain threshold, PTo : pain tolerance, PR : pain rating on visual analog scale.
As per the above results, pain threshold was found to be significantly more in boys compare to girls (22.72 ±
8.96 vs 17.68 ± 6.59). Pain tolerance was also found to be significantly more in boys compare to girls (66.92 ±
22.32 vs 50.98 ± 15.40). While pain rating on visual analog scale was found to be significantly more in girls
compare to boys (6.58 ± 0.90 vs 6.0 ± 0.83). There was no difference in baseline pulse between boys and girls
while pulse reactivity was found to be significantly more in girls compare to boys (12.58 ± 7.86 vs 7.0 ± 6.25).

                     Chart 1: Difference in various parameters between male and female.
                         78.9477.58
                    80                                  66.92
                    60                                        50.98

                    40                           22.72                                 male
                                                     17.68
                                         12.58
                    20                  7                             6 6.58           female
                      0
                           pulse       pulse       pain      pain    pain
                                     reactivity threshold tolerance rating


                                                        2
Sex related difference in response to experimental pain in first year medical students


Data was also analysed by zero order correlation coefficient to determine relation between baseline pulse with
pain sensitivity parameters and pulse reactivity with pain sensitivity parameters in both male and female.

                                  Table 2: correlation coefficients in male data
          Parameters               Pain threshold         Pain tolerance              Pain rating
          Baseline Pulse           r = 0.251              r = 0.194                   r = -0.069
                                   p = 0.0787             p = 0.1752                  p = 0.6317
           Pulse reactivity        r = -0.045             r = 0.044                   r = -0.227
                                   p = 0.7539             p = 0.7594                  p = 0.1127
Data demonstrate r value between parameters.
* Correlation significant at p<0.05 (two-tailed)

                                  Table 3: correlation coefficients in female data
           Parameters              Pain threshold          Pain tolerance            Pain rating
           Baseline Pulse          r = 0.181               r = 0.112                 r = -0.133
                                   p = 0.2085              p = 0.4368                p = 0.3540
           Pulse reactivity        r = -0.144              r = 0.0086                r = -0.117
                                   p = 0.3173              p = 0.9522                p = 0.4185
Data demonstrate r value between parameters.
* Correlation significant at p<0.05 (two-tailed)

         As per the above results of table 2 and table 3, Baseline pulse was found to be positively correlated
with pain threshold and pain tolerance in both sexes while negatively correlated with pain rating in both sexes.
Second observation is that pulse reactivity was found to be positively correlated with pain tolerance in both
sexes while negatively correlated with pain threshold and pain rating in both sexes. None of the correlations
were found to be significant in this study.

               Chart 2: correlation between baseline pulse and pain threshold in male and female
                              40

                              35

                              30

                              25
                  PTh (sec)




                                                                                     male
                              20
                                                                                     female
                              15                                                     Linear (male)
                                                                                     Linear (female)
                              10

                               5

                               0
                                   60   70         80           90   100
                                             pulse (rate/min)




                                                           3
Sex related difference in response to experimental pain in first year medical students

                Chart 3: correlation between baseline pulse and pain tolerance in male and female

                                    90



                     Pto (sec)
                                    70
                                                                                         male
                                    50
                                                                                         female
                                    30
                                         60    70          80     90   100
                                                   pulse (rate/min)


                 Chart 4: correlation between baseline pulse and pain rating in male and female
                                    8

                                    7
                      pain rating




                                                                                     male
                                    6
                                                                                     female
                                    5
                                                                                     Linear (male)
                                    4                                                Linear (female)
                                        60    70          80      90   100
                                               pulse (rate/min)


                                                     V.         DISCUSSION
         Women typically displaying greater pain sensitivity than men, but the mechanisms underlying these
differences remain unclear. One possible explanation suggests that men are more motivated to tolerate and
suppress expressions of pain because of the masculine sex role, whereas the feminine sex role encourages pain
expression and produces lower motivation to tolerate pain among women (7).
         Other mechanisms have been proposed to explain the differing response to experimental pain between
the sexes, including hormonal factors, differences in pain modulatory systems, and genetic factors. From a more
psychosocial perspective, another potential explanation for the sex difference in pain responses involves social
role expectancies. Different pain perception might account for sex difference in pulse reactivity. Hormonal
influences may play a minor role (8).
         In this study, we found an insignificant inverse relationship between baseline pulse and pain sensitivity
as indicated by pain threshold and pain tolerance. This relation was also found by Cynthia d. Myers et al. (7), and
Otto and Dougher in their studies (9).
                                                          REFERENCES
  [1].  Abu-Saad Huijer H. Chronic pain: A review. Leb Med J. 2010;58(1):21-27
  [2].  IASP Sub-committee on Taxonomy. Pain terms: a list with definitions and notes on usage. Pain 1980; 8: 249-52.
  [3].  Daniel lowery, ma, roger b. Fillingim, phd, and rex a. Wright, phd: sex differences and incentive effects on
        perceptual and cardiovascular responses to cold pressor pain. Psychosomatic medicine 65:284–291 (2003)
  [4].  Ritesh M., Karia M. D., Mahavirsingh Rajput M. D., Hemant B., Mehta M. D., Pradnya A. and Gokhale M. D.:
        Normal Young Healthy Subjects: A Prediction of Future Possibilities of Hypertension. J Phys Pharm Adv 2012,
        2(6): 223-226
  [5].  Mitchell LA, MacDonald RA, Brodie EE: Temperature and the cold pressor test. J Pain 5:233-237, 2004
  [6].  Dr. Muralidhar Joshi: Evaluation of pain. Indian J. Anaesth. 2006; 50 (5) : 335 – 339.
  [7].  Cynthia d. Myers, phd, michael e. Robinson, phd, joseph l. Riley iii, phd, and david sheffield, phd sex, gender, and
        blood pressure: contributions to experimental pain report psychosomatic medicine 63:545–550 (2001)
  [8].  Berkley kj. Sex differences in pain. Behav brain sci 1997;20: 371–80.
  [9].  Otto MW, Dougher MJ. Sex differences and personality factors in responsivity to pain, Percept Mot Skills
        1985;61:383–90.
  [10]. Woodrow KM, Friedman GD, Siegelaub AB, Collen MF. Pain tolerance: differences according to age, sex and
        race. Psychosom Med 1972; 34: 548–56.

                                                                 4

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IOSR Journal of Pharmacy (IOSRPHR), www.iosrphr.org, call for paper, research paper publishing, where to publish research paper, journal publishing, how to publish research paper, Call for research paper, international journal, publishing a paper, call fo

  • 1. IOSR Journal of Pharmacy e-ISSN: 2250-3013, p-ISSN: 2319-4219, www.iosrphr.org Volume 2 Issue 6 ‖‖ Nov-Dec. 2012 ‖‖ PP.01-04 Sex related difference in response to experimental pain in first year medical students Samir Mendpara1 Veena Jasuja2 Geetanjali Purohit3 BM Palan4 JM Harsoda5 1 Dr.Samir Mendpara (Resident doctor in Physiology) 2 Dr. Veena Jasuja (Tutor in Physiology) 3 Ms. Geetanjali Purohit: (Tutor in Physiology) 4 Dr. BM Palan: (Associate Professor in Physiology) 5 Dr.JM Harsoda: (Prof & Head in Physiology) SBKS MI & RC, Sumandeep Vidyapeeth, Vadodara, Gujarat Abstract––Pain is complex multidimensional experience influenced by physical, psychological, and social factors. In recent years sex differences in responses to pain have received increased attention. Purpose of study was to determine sex differences in experimental pain response. For this study cold pressor test was used to exert experimental pain. 100 medical students (50 boys and 50 girls) participated in study. Subject was asked to submit his hand into container with ice water. Radial pulse was measured before and immediately after test to determine pulse reactivity. Pain threshold and tolerance were measured. Subject was asked to determine intensity of pain during test and rate on VAS. Data was statistically analysed using student t-test and Correlation Coefficient. Pain threshold and pain tolerance were significantly more in boys, Pain rating was significantly more in girls. Pain reactivity was significantly more in girls. In both sexes, baseline pulse showed positive relationship with pain threshold and pain tolerance and negative relationship with pain rating. Women typically displaying greater pain sensitivity than men, but mechanisms underlying differences remain unclear. Possible explanation suggests that men are more motivated to tolerate and suppress expressions of pain because masculine sex role, whereas feminine sex role encourages pain expression. Different pain perception might account for sex difference in pulse reactivity. Hormonal influences may play minor role. I. INTRODUCTION Pain is the main reason for visiting the emergency department in more than 50% of cases and is present in 30% of family practice visits. Several epidemiological studies from different countries have reported widely varying prevalence rates for chronic pain, ranging from 12-80% of the population (1). The International Association for the Study of Pain's widely used definition states: "Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage" (2). Pain is a complex multidimensional experience influenced by physical, psychological, and social factors. In recent years sex differences in responses to pain have received increased attention. Multiple studies have investigated sex differences in experimental pain perception using a wide variety of noxious stimuli (3). For this study, the cold pressor test was used to exert experimental pain. The cold pressor test (CPT) is an empirically validated test commonly used in research on stress, pain and cardiovascular reactivity. George E. Brown and Edgar A. Hines in 1932 introduced a test designed to detect latent states of hypertension by immersion of one extremity in ice water for 1-3 minutes. This test was called as Hines and Brown test. Later on name of this test was changed to cold pressor test. Cold pressure test is simple, provocative, non-invasive, reliable and cheap test to know autonomic status of body (4). If variation in response to experimental pain according to age, sex, race etc, is studied, it is quite possible that more effective analgesia could be developed on the basis of these differences. II. AIM AND OBJECTIVE The purpose of this study was to determine sex differences in experimental pain response. For this study pain threshold, pain tolerance and pain rating as three pain sensitivity parameters and radial pulse as cardiovascular parameter were selected to study the response of experimental pain. 1
  • 2. Sex related difference in response to experimental pain in first year medical students III. MATERIALS & METHODS Total 100 young volunteers, medical students of S.B.K.S. medical college and research centre participated as subject in this study. 100 students were taken in two groups. First was group of 50 male students and second was group of 50 female students. The present study was conducted in clinical laboratory, Department of Physiology, S.B.K.S. medical college. Written informed consent was obtained according to ethical committee policy. On the day of testing, the subject signed an consent form acknowledging their willingness to participate in the study. Before testing, every subject was interviewed for recent history and examined for respiratory disease and cardio-vascular disease and subjects with such type of diseases were excluded from the study. Person taking analgesic for pain relief was excluded from the study. Subjects were asked to sit comfortably in chairs. After rest for around 10 minutes, resting radial pulse was counted for one minute and recorded as rate per minute. Laboratory water bath was filled with ice cold water and temperature of cold water was measured using laboratory thermometer. Temperature of cold water was maintained between 4˚ C to 8˚ C by adding required ice cold water to the container (5). After that, subject was asked to submit his/her dominant hand into a container with ice water (palm down, up to 5 cm above wrist level). Immediately, two stop watches were started. Subject was asked to determine intensity of pain during test and rate it on a scale of 0 to 10 and for that subject was explained that Zero represents no pain at all while 10 represents the worst imaginable pain (6). Subject was explained that once pain was present during test, they let the researcher know. One stop watch was stopped. This provided pain threshold (first feeling pain). Once the pain was unbearable, the participant removed his/her hand, second stop watch was stopped and this provided pain tolerance. Immediately after test radial pulse rate per minute was measured. Statistical analysis: Data was collected and statistical analysed using student t test and zero order correlation coefficient. IV. OBSERVATION AND RESULTS Table 1: Difference in various parameters between male and female. Parameters Male Female T value P value Pulse (rate/min) 78.94 ± 7.05 77.58 ± 7.54 0.98 0.35 Pulse reactivity 7.0 ± 6.25 12.58 ± 7.86 3.92 0.0001** PTh (sec) 22.72 ± 8.96 17.68 ± 6.59 3.2 0.001** PTo (sec) 66.92 ± 22.32 50.98 ± 15.40 4.15 0.043* PR (VAS) 6.0 ± 0.83 6.58 ± 0.90 3.33 0.001** Data is demonstrated in MEAN ± SD. unpaired t-test, df : 98 * Difference significant at p<0.05 ** Difference highly significant at p<0.01 Pulse reactivity = after CPT pulse – Baseline pulse. PTh: pain threshold, PTo : pain tolerance, PR : pain rating on visual analog scale. As per the above results, pain threshold was found to be significantly more in boys compare to girls (22.72 ± 8.96 vs 17.68 ± 6.59). Pain tolerance was also found to be significantly more in boys compare to girls (66.92 ± 22.32 vs 50.98 ± 15.40). While pain rating on visual analog scale was found to be significantly more in girls compare to boys (6.58 ± 0.90 vs 6.0 ± 0.83). There was no difference in baseline pulse between boys and girls while pulse reactivity was found to be significantly more in girls compare to boys (12.58 ± 7.86 vs 7.0 ± 6.25). Chart 1: Difference in various parameters between male and female. 78.9477.58 80 66.92 60 50.98 40 22.72 male 17.68 12.58 20 7 6 6.58 female 0 pulse pulse pain pain pain reactivity threshold tolerance rating 2
  • 3. Sex related difference in response to experimental pain in first year medical students Data was also analysed by zero order correlation coefficient to determine relation between baseline pulse with pain sensitivity parameters and pulse reactivity with pain sensitivity parameters in both male and female. Table 2: correlation coefficients in male data Parameters Pain threshold Pain tolerance Pain rating Baseline Pulse r = 0.251 r = 0.194 r = -0.069 p = 0.0787 p = 0.1752 p = 0.6317 Pulse reactivity r = -0.045 r = 0.044 r = -0.227 p = 0.7539 p = 0.7594 p = 0.1127 Data demonstrate r value between parameters. * Correlation significant at p<0.05 (two-tailed) Table 3: correlation coefficients in female data Parameters Pain threshold Pain tolerance Pain rating Baseline Pulse r = 0.181 r = 0.112 r = -0.133 p = 0.2085 p = 0.4368 p = 0.3540 Pulse reactivity r = -0.144 r = 0.0086 r = -0.117 p = 0.3173 p = 0.9522 p = 0.4185 Data demonstrate r value between parameters. * Correlation significant at p<0.05 (two-tailed) As per the above results of table 2 and table 3, Baseline pulse was found to be positively correlated with pain threshold and pain tolerance in both sexes while negatively correlated with pain rating in both sexes. Second observation is that pulse reactivity was found to be positively correlated with pain tolerance in both sexes while negatively correlated with pain threshold and pain rating in both sexes. None of the correlations were found to be significant in this study. Chart 2: correlation between baseline pulse and pain threshold in male and female 40 35 30 25 PTh (sec) male 20 female 15 Linear (male) Linear (female) 10 5 0 60 70 80 90 100 pulse (rate/min) 3
  • 4. Sex related difference in response to experimental pain in first year medical students Chart 3: correlation between baseline pulse and pain tolerance in male and female 90 Pto (sec) 70 male 50 female 30 60 70 80 90 100 pulse (rate/min) Chart 4: correlation between baseline pulse and pain rating in male and female 8 7 pain rating male 6 female 5 Linear (male) 4 Linear (female) 60 70 80 90 100 pulse (rate/min) V. DISCUSSION Women typically displaying greater pain sensitivity than men, but the mechanisms underlying these differences remain unclear. One possible explanation suggests that men are more motivated to tolerate and suppress expressions of pain because of the masculine sex role, whereas the feminine sex role encourages pain expression and produces lower motivation to tolerate pain among women (7). Other mechanisms have been proposed to explain the differing response to experimental pain between the sexes, including hormonal factors, differences in pain modulatory systems, and genetic factors. From a more psychosocial perspective, another potential explanation for the sex difference in pain responses involves social role expectancies. Different pain perception might account for sex difference in pulse reactivity. Hormonal influences may play a minor role (8). In this study, we found an insignificant inverse relationship between baseline pulse and pain sensitivity as indicated by pain threshold and pain tolerance. This relation was also found by Cynthia d. Myers et al. (7), and Otto and Dougher in their studies (9). REFERENCES [1]. Abu-Saad Huijer H. Chronic pain: A review. Leb Med J. 2010;58(1):21-27 [2]. IASP Sub-committee on Taxonomy. Pain terms: a list with definitions and notes on usage. Pain 1980; 8: 249-52. [3]. Daniel lowery, ma, roger b. Fillingim, phd, and rex a. Wright, phd: sex differences and incentive effects on perceptual and cardiovascular responses to cold pressor pain. Psychosomatic medicine 65:284–291 (2003) [4]. Ritesh M., Karia M. D., Mahavirsingh Rajput M. D., Hemant B., Mehta M. D., Pradnya A. and Gokhale M. D.: Normal Young Healthy Subjects: A Prediction of Future Possibilities of Hypertension. J Phys Pharm Adv 2012, 2(6): 223-226 [5]. Mitchell LA, MacDonald RA, Brodie EE: Temperature and the cold pressor test. J Pain 5:233-237, 2004 [6]. Dr. Muralidhar Joshi: Evaluation of pain. Indian J. Anaesth. 2006; 50 (5) : 335 – 339. [7]. Cynthia d. Myers, phd, michael e. Robinson, phd, joseph l. Riley iii, phd, and david sheffield, phd sex, gender, and blood pressure: contributions to experimental pain report psychosomatic medicine 63:545–550 (2001) [8]. Berkley kj. Sex differences in pain. Behav brain sci 1997;20: 371–80. [9]. Otto MW, Dougher MJ. Sex differences and personality factors in responsivity to pain, Percept Mot Skills 1985;61:383–90. [10]. Woodrow KM, Friedman GD, Siegelaub AB, Collen MF. Pain tolerance: differences according to age, sex and race. Psychosom Med 1972; 34: 548–56. 4