ORIGINAL ARTICLE

Relevance of Water Temperature, Apparatus, and Age to Children’s Pain during the Cold Pressor Task Kathryn A. Birnie, BA (Hons)*,†; Jennifer A. Parker, PhD†; Christine T. Chambers, PhD*,†,‡ *Department of Psychology and Neuroscience, Dalhousie University, Halifax, Nova Scotia ; Centre for Pediatric Pain Research, IWK Health Centre, Halifax, Nova Scotia ; ‡Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada

†

& Abstract Background: Effective use of experimental pain in research depends on a thorough understanding of factors influencing their use. Although studies using the cold pressor task (CPT) have critically advanced our knowledge of pain mechanisms, assessment, and management in adults and children, the impact of identified methodological variability in its use is not known (ie, water temperature and apparatus); furthermore, whether methodological variations differentially impact children across development. Methods: Pain outcomes were examined in 113 healthy children from three age groups (8- to 9-, 10- to 11-, and 12- to 14-year-olds) who completed three CPTs at different water temperatures (5, 7, 10°C) in counterbalanced order. Children were randomly assigned to one of two apparatus (ice- vs. electric-cooled) for all CPTs. Children’s hand was warmed to its baseline temperature between CPTs. Results: Colder water (2 to 3°C decreases) was associated with significantly higher pain intensity and unpleasantness, and lower pain tolerance and threshold. Older children (12 to Address correspondence and reprint requests to: Kathryn A. Birnie, BA (Hons), Centre for Pediatric Pain Research (West), K8536 (8th floor, Children’s site), IWK Health Centre, 5850/5980 University Avenue, Halifax, NS, B3K 6R8 Canada. E-mail: [email protected]. Submitted: April 22, 2014; Revised: August 27, 2014; Revision accepted: September 1, 2014 DOI. 10.1111/papr.12257

© 2014 World Institute of Pain, 1530-7085/16/$15.00 Pain Practice, Volume 16, Issue 1, 2016 46–56

14 years) reported significantly worse pain intensity and unpleasantness as compared to 8- to 9-year-olds, likely due to longer pain tolerance. Pain outcomes in 10- to 11-year-olds fell between the other age groups, with significant differences for pain unpleasantness and pain tolerance (at 10°C). Higher pain-related fear and pain unpleasantness occurred with the electric-cooled apparatus. Girls had higher pain tolerance and threshold at all temperatures. Conclusions: These results provide critically important information about water temperature, apparatus, and child age on CPT pain responding. It informs design of future CPT studies and directs consideration of methodological variability and child age when interpreting study findings. & Key Words: cold pressor task, CPT, pediatric pain, experimental pain, methods, children, adolescents, age, sex

INTRODUCTION Effective use of experimental pain depends on a thorough understanding of the factors that influence their use. Although different experimental pain modalities represent distinct dimensions of pain perception1 and are differentially impacted by genetic vs. environmental factors,2 researchers may make inappropriate claims about findings if the impact of methodological variability within these paradigms is not known. The cold pressor task (CPT) has a long-standing history in experimental pain research with adults3 and

CPT Temperature, Apparatus, and Child Age  47

children4 and continues to play a key role in advancing our knowledge of pain mechanisms, assessment, and management.5,6 Despite being the most widely used experimental pain with children, a recent review highlighted significant methodological variability in its use.7 Particularly, variability in water temperature (5 to 13°C) and type of apparatus (ice vs. electric-cooled), two areas believed to contribute to inconsistent findings across studies.8 Pediatric CPT guidelines recommend 10°C water; however, studies using this temperature report large proportions of children reaching maximum allowable immersion times (3 or 4 minutes).9,10 This produces a ceiling effect in pain tolerance, limiting its value as an outcome in some studies. In response, some pediatric researchers have used colder water (5 to 7°C),11–13 approaching temperatures used with adults (0 to 4°C).14 Although some studies have revealed a significant impact of 2 to 5°C differences in CPT water temperature on adults’ pain responding,6,14 others have not found such differences.15 Furthermore, temperatures used with children have been associated with differential pain responding to other experimental cold stimuli,16,17 suggesting that pain may be processed and experienced differently at varying water temperatures. CPT apparatus varies in method of cooling, control of water temperature and circulation rate. While the electric-cooled apparatus was recommended by consensus of pediatric researchers,8 it is significantly more costly ($4,000 to 6,000 vs. $200 to 300USD), which may explain continued use of an ice-cooled version.7 The impact of CPT apparatus is unknown in adults or children, but has been speculated to contribute to inconsistent findings relating to the impact of water temperature on pain outcomes.15 Although age differences in experimental pain are reported in children,12,18 the impact of age on CPT responses has not been adequately addressed. The ethical appropriateness of research is judged, in part, by minimization of harm and may depend on the interplay between child age and CPT procedures (eg, water temperature).19 Use of the CPT with children as young as 3 years,20 coupled with the trend toward colder water, could pose significant ethical concerns if not appropriately investigated. This study examined the impact of CPT water temperature (5, 7, 10°C) and type of apparatus (icevs. electric-cooled) on pain-related outcomes in children (8- to 9-, 10- to 11-, and 12- to 14-year-olds). Greater

pain intensity and unpleasantness, and decreased pain tolerance and threshold were expected with colder water. Older children were expected to have greater pain tolerance.

METHODS Participants Participants included 113 healthy children (54 boys) aged 8 to 14 years (M = 10.96; SD = 2.03) recruited through community postings and advertisement. The number of children per age group was 40 (8- to 9-yearolds), 37 (10- to 11-year-olds), and 36 (12- to 14-yearolds). Participant demographics are presented in Table 1. Children were excluded if they had current or past history of chronic illness or chronic pain, had a developmental delay, had previously completed the CPT, or if participation in the CPT was contraindicated (eg history of cardiovascular disorder).21 Three additional participations were excluded because of previously unreported chronic pain, not immersing their hand fully in the water for all CPTs, and for monitoring the time during the CPT. Procedure Children were accompanied by one parent/guardian who provided written consent. All children provided assent and were identified by a unique participant number. Children received $10CAD and a certificate to thank them for participation; parents received $5CAD for parking/transportation costs. The study was approved by the hospital’s research ethics board. Prior to any CPT immersions, the child’s height, weight, and baseline hand temperature were measured by a research assistant. Hand temperature was measured by a digital thermometer for skin temperature accurate to 0.5°C (HoMedics No-Touch Thermometer; model TI-150-ACA). During one session, children completed a series of three CPTs with differing water temperature (5, 7, and 10°C). These temperatures were selected as they reflect guidelines for use of the CPT in pediatric research (ie, 10°C),21 the second most commonly used water temperature in pediatric CPT research as noted in our recent systematic review (ie, 5°C),7 and one temperature in between these extremes that has been used in previous research (ie, 7°C).11,22 The order of CPTs at differing water temperatures was counterbalanced, such that all

CPT Temperature, Apparatus, and Child Age  49

with a 120v submersible fountain pump that circulates the water between compartments at a rate of 200 L/hour. Ice is placed in the compartment adjacent to where the child submerses their hand to cool the water to the appropriate temperature. This type of CPT apparatus is reported to keep the water temperature stable within  1.0°C. Three identical ice-cooled apparatus were used with each set to one of the three water temperatures. Electric-Cooled Cold Pressor. The electric-cooled CPT apparatus (Techne© www.techne.com) consists of an 8L capacity stainless steel tank filled with cold water. The water is circulated at 10L/minute using an external pump attached to the tank. The cold pressor cools the water using a dip cooler and contains an electric thermoregulator that keeps the water temperature stable to within  0.1°C. One electric-cooled apparatus was used for all three water temperatures. Measures Children’s height and weight were measured by a research assistant. Parents reported on other child demographics (ie, birth date, ethnicity), as well as child pubertal status using the Pubertal Development Scale (PDS).23 This measure includes 3 items regarding growth spurt, body hair, and skin changes, with 2 additional items, respectively, relevant to only males (ie, facial hair and voice change) or females (ie, breast development and menarche). Pain-related Outcomes. Immediately before completing each CPT, children were asked to rate how nervous they felt (ie, state anxiety) using a 100 mm visual analogue scale. Children’s pain threshold was solicited by asking them to indicate when their hand first began to feel uncomfortable or hurt by saying “it hurts now” to the research assistant. Pain threshold was considered the amount of time elapsed between initial submersion of their hand in cold water and their verbal report of first pain. Immediately following each CPT, children rated the intensity of worst and average pain using the Faces Pain Scale-Revised (FPS-R).24 The FPS-R consists of six faces from 0 “no pain” to 10 “very much pain.” It is a well-validated self-report measure used to assess children’s pain.25 Children rated pain-related fear using the Children’s Fear Scale, which is a validated and reliable scale consisting of five faces from 0 “not scared at all” to 4 “most scared possible.”26 Children

also rated pain unpleasantness using the Facial Affective Scale,27,28 which is comprised of nine faces ranging from happy to sad that are coded using affective magnitude ratings from 0.04 to 0.97. The scale has good convergent validity.29 Pain tolerance was considered the time elapsed between initial submersion of the child’s hand in cold water until its removal (or the 4 minute maximum allowable immersion time, if reached). Following completion of all CPTs, children were asked the following three openended questions: “Which cold water task felt the most cold?”, “Which cold water task felt the least cold?”, “Did you do anything to help you keep your hand in the water longer?” Data Analysis A series of 3 (water temperature: 5, 7, 10°C) 9 2 (CPT apparatus: ice- vs. electric-cooled) 9 3 (age group: 8- to 9-year-olds; 10- to 11-year-olds; 12- to 14-year-olds) repeated-measures mixed ANOVAs were conducted with average and worst pain intensity, pain tolerance, pain threshold, and pain unpleasantness as dependent variables. Planned pairwise comparisons and simple main effects tests were conducted as needed to follow-up on significant main effects or interactions. Order effects were considered to ensure that any findings relating to water temperature were not a result of the order in which water temperatures were presented. Independent samples t-tests were used to explore the influence of child sex on pain outcomes. A content analysis was used to categorize children’s responses to the three openended questions.

RESULTS Fifty-three children were randomized to the ice-cooled cold pressor apparatus, and 60 to the electric-cooled cold pressor apparatus. All analyses are based on the total sample of 113 children with the exception of analyses examining pain threshold. Twenty-eight children are excluded only from analyses using pain threshold as they did not indicate their pain threshold during one or more of the CPT immersions. Thus, analyses using pain threshold are based on a subsample of 85 children (n = 28, 8- to 9-year-olds; n = 29, 10- to 11-year-olds; n = 28, 12- to 14-year-olds). Of these, 41 were boys. Children’s spontaneous reporting of pain threshold was not related to child age (t = 0.759, P = 0.449).

CPT Temperature, Apparatus, and Child Age  49

with a 120v submersible fountain pump that circulates the water between compartments at a rate of 200 L/hour. Ice is placed in the compartment adjacent to where the child submerses their hand to cool the water to the appropriate temperature. This type of CPT apparatus is reported to keep the water temperature stable within  1.0°C. Three identical ice-cooled apparatus were used with each set to one of the three water temperatures. Electric-Cooled Cold Pressor. The electric-cooled CPT apparatus (Techne© www.techne.com) consists of an 8L capacity stainless steel tank filled with cold water. The water is circulated at 10L/minute using an external pump attached to the tank. The cold pressor cools the water using a dip cooler and contains an electric thermoregulator that keeps the water temperature stable to within  0.1°C. One electric-cooled apparatus was used for all three water temperatures. Measures Children’s height and weight were measured by a research assistant. Parents reported on other child demographics (ie, birth date, ethnicity), as well as child pubertal status using the Pubertal Development Scale (PDS).23 This measure includes 3 items regarding growth spurt, body hair, and skin changes, with 2 additional items, respectively, relevant to only males (ie, facial hair and voice change) or females (ie, breast development and menarche). Pain-related Outcomes. Immediately before completing each CPT, children were asked to rate how nervous they felt (ie, state anxiety) using a 100 mm visual analogue scale. Children’s pain threshold was solicited by asking them to indicate when their hand first began to feel uncomfortable or hurt by saying “it hurts now” to the research assistant. Pain threshold was considered the amount of time elapsed between initial submersion of their hand in cold water and their verbal report of first pain. Immediately following each CPT, children rated the intensity of worst and average pain using the Faces Pain Scale-Revised (FPS-R).24 The FPS-R consists of six faces from 0 “no pain” to 10 “very much pain.” It is a well-validated self-report measure used to assess children’s pain.25 Children rated pain-related fear using the Children’s Fear Scale, which is a validated and reliable scale consisting of five faces from 0 “not scared at all” to 4 “most scared possible.”26 Children

also rated pain unpleasantness using the Facial Affective Scale,27,28 which is comprised of nine faces ranging from happy to sad that are coded using affective magnitude ratings from 0.04 to 0.97. The scale has good convergent validity.29 Pain tolerance was considered the time elapsed between initial submersion of the child’s hand in cold water until its removal (or the 4 minute maximum allowable immersion time, if reached). Following completion of all CPTs, children were asked the following three openended questions: “Which cold water task felt the most cold?”, “Which cold water task felt the least cold?”, “Did you do anything to help you keep your hand in the water longer?” Data Analysis A series of 3 (water temperature: 5, 7, 10°C) 9 2 (CPT apparatus: ice- vs. electric-cooled) 9 3 (age group: 8- to 9-year-olds; 10- to 11-year-olds; 12- to 14-year-olds) repeated-measures mixed ANOVAs were conducted with average and worst pain intensity, pain tolerance, pain threshold, and pain unpleasantness as dependent variables. Planned pairwise comparisons and simple main effects tests were conducted as needed to follow-up on significant main effects or interactions. Order effects were considered to ensure that any findings relating to water temperature were not a result of the order in which water temperatures were presented. Independent samples t-tests were used to explore the influence of child sex on pain outcomes. A content analysis was used to categorize children’s responses to the three openended questions.

RESULTS Fifty-three children were randomized to the ice-cooled cold pressor apparatus, and 60 to the electric-cooled cold pressor apparatus. All analyses are based on the total sample of 113 children with the exception of analyses examining pain threshold. Twenty-eight children are excluded only from analyses using pain threshold as they did not indicate their pain threshold during one or more of the CPT immersions. Thus, analyses using pain threshold are based on a subsample of 85 children (n = 28, 8- to 9-year-olds; n = 29, 10- to 11-year-olds; n = 28, 12- to 14-year-olds). Of these, 41 were boys. Children’s spontaneous reporting of pain threshold was not related to child age (t = 0.759, P = 0.449).

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As per study protocol, water temperature for the CPT immersions stayed within  1.0°C of the designated water temperature of 5°C (4.0 to 5.5°C), 7°C (6.7 to 7.6°C), and 10°C (9.7 to 10.6°C) as measured before and after each child’s hand submersion. The change in water temperature from before the child’s hand immersion to after the removal of their hand from the water was minimal in the ice-cooled cold pressor at 5°C (M = 0.18; SD = 0.11, range = 0.00 to 0.50), 7°C (M = 0.12; SD = 0.12, range = 0.40 to 0.30), and 10°C (M = 0.14; SD = 0.10, range = 0.00 to 0.40), as well as the electric-cooled cold pressor at 5°C (M = 0.05; SD = 0.18, range = 1.00 to 0.30), 7°C (M = 0.06; SD = 0.12, range = 0.10 to 0.60), and 10°C (M = 0.08; SD = 0.13, range = 0.20 to 0.50). Children’s baseline hand temperature ranged from 27.5 to 34.4°C (M = 31.90; SD = 1.38). Children’s hand temperature was within  1.0°C of their baseline hand temperature after submission in a warm water bath prior to subsequent CPT immersions (M = 0.00, SD = 0.77 prior to second CPT; M = 0.25, SD = 0.75 prior to third CPT). Children’s hand temperature after each CPT was as follows: 5°C (M = 18.71; SD = 3.19; range = 13.60 to 28.10), 7°C (M = 19.04; SD = 2.86; range = 14.60 to 27.00), and 10°C (M = 20.02; SD = 2.06; range = 15.60 to 25.50). Postimmersion hand temperatures were significantly influenced by water temperature (F[2, 222] = 39.93, P < 0.01), but not by type of CPT apparatus (F[1, 111] = 1.43, P = 0.23). Pre-CPT State Anxiety As state anxiety was assessed prior to hand immersion and children were not aware of CPT water temperature, children’s pre-CPT state anxiety was analyzed based on order of CPT immersions, irrespective of water temperature order. A 3 (CPT immersion order: CPT1, CPT2, CPT3) 9 2 (CPT apparatus: ice- vs. electric-cooled) 9 3 (age group: 8- to 9-year-olds; 10- to 11-year-olds; 12- to 14-year-olds) repeated-measures mixed ANOVA revealed no main effect of CPT order (F[2, 214] = 2.42, P = 0.09), CPT apparatus (F[1, 107] = 0.072, P = 0.79), or age group (F[2, 107] = 2.33, P = 0.10). Children’s mean pre-CPT state anxiety was stable across CPT1 (M = 25.27, SD = 21.62), CPT2 (M = 25.22, SD = 23.50), and CPT3 (M = 21.36, SD = 25.23). Altogether, this indicates that children’s pre-CPT state anxiety was relatively low and was not influenced by whether it was the first or subsequent CPT immersions,

the type of CPT apparatus, or the age of the child. Furthermore, it suggests that pre-CPT state anxiety was not differentially impacting pain responding based on CPT immersion order. Descriptives See Table 2 for the means and standard deviations for pain outcomes for CPT water temperature (5, 7, 10°C) by type of CPT apparatus (ice- vs. electric-cooled) and by age group (8- to 9-year-olds, 10- to 11-year-olds, 12to 14-year-olds). Order Effects As children were randomly assigned to view 1 of 6 possible orders of CPT water temperatures, a series of 6 (temperature order) 9 2 (CPT apparatus) 9 3 (age group) repeated-measures ANOVAs were conducted to determine whether pain outcomes differed based on which water temperature order was experienced. Results revealed a significant main effect of water temperature order for pain-related fear (F[5,77] = 3.35, P < 0.01). Pairwise comparisons indicated that children who completed CPT immersions in the order 7°C - 10°C - 5°C reported significantly lower painrelated fear (M = 0.35; SD = 0.59) than children who completed CPT immersions in the order 10°C - 7°C 5°C (M = 1.30; SD = 1.34). No other significant differences were noted on pain-related fear based on water temperature order. To account for this significant finding, water temperature order was entered as a covariate in subsequent analyses involving pain-related fear. No significant differences between water temperature order were reported for average (F[5, 77] = 1.38, P = 0.24) and worst (F[5, 77] = 2.27, P = 0.06) pain intensity, pain tolerance (F[5, 77] = 0.80, P = 0.56), pain unpleasantness (F[5, 77] = 1.53, P = 0.19), or pain threshold (F[5, 52] = 0.19, P = 0.97). Pain Intensity Worst Pain. Analyses revealed a significant main effect of water temperature, F(2, 214) = 34.12, P < 0.01 on worst pain intensity. Planned pairwise comparisons revealed that worst pain intensity was significantly higher at 5°C than at 7°C and 10°C, and significantly higher at 7°C as compared to 10°C. This indicates that as water temperature decreased, worst pain intensity increased. There was also a significant main effect of age

CPT Temperature, Apparatus, and Child Age  51

Table 2. Means and Standard Deviations for Pain Outcomes at Three CPT Temperatures by Cold Pressor Apparatus and by Age Group 5°C M (SD) Ice-Cooled CPT Worst pain 8- to 9-year-olds 10- to 11-year-olds 12- to 14-year-olds Total Average pain 8- to 9-year-olds 10- to 11-year-olds 12- to 14-year-olds Total Pain tolerance 8- to 9-year-olds 10- to 11-year-olds 12- to 14-year-olds Total Pain threshold* 8- to 9-year-olds 10- to 11-year-olds 12- to 14-year-olds Total Pain unpleasantness 8- to 9-year-olds 10- to 11-year-olds 12- to 14-year-olds Total Pain-related fear 8- to 9-year-olds 10- to 11-year-olds 12- to 14-year-olds Total

7°C M (SD) Electric-Cooled CPT

10°C M (SD)

Ice-Cooled CPT

Electric-Cooled CPT

Ice-Cooled CPT

Electric-Cooled CPT

6.00 5.18 6.05 5.75

(3.43) (2.24) (2.01) (2.56)

4.58 5.80 6.63 5.53

(2.67) (2.24) (2.03) (2.48)

4.38 (3.03) 4.59 (1.84) 5.80 (2.24) 4.98 (2.44)

4.67 (2.68) 5.10 (2.71) 6.38 (2.09) 5.27 (2.60)

3.25 (2.41) 3.18 (2.01) 4.50 (1.93) 3.70 (2.16)

3.58 (2.43) 4.00 (2.05) 5.13 (2.42) 4.13 (2.35)

5.00 3.65 4.60 4.42

(3.27) (2.37) (1.73) (2.49)

4.17 4.50 4.38 4.33

(2.57) (2.59) (1.67) (2.33)

3.63 (3.03) 2.94 (1.89) 4.80 (1.99) 3.85 (2.41)

4.50 (2.30) 3.50 (2.59) 4.50 (1.71) 4.17 (2.28)

3.00 (2.73) 1.88 (1.80) 3.00 (2.00) 2.64 (2.21)

3.50 (2.45) 3.00 (2.38) 3.00 (1.93) 3.20 (2.28)

88.50 100.79 158.00 118.67

(105.96) (95.62) (99.92) (103.34)

67.29 100.46 117.75 91.80

(92.30) (96.51) (105.40) (97.96)

91.81 (103.76) 136.47 (95.92) 171.80 (95.72) 136.32 (101.87)

76.21 (97.11) 122.05 (100.93) 114.25 (101.70) 101.63 (100.17)

101.19 169.66 195.45 158.72

(98.63) (97.48) (79.32) (98.01)

91.29 (98.93) 161.35 (99.96) 142.83 (101.58) 128.39 (103.16)

12.36 21.50 20.93 18.40

(10.38) (15.76) (16.08) (14.61)

13.94 19.74 17.29 17.08

(13.62) (21.05) (17.96) (17.75)

16.82 (10.35) 22.70 (13.43) 25.50 (20.83) 21.97 (16.09)

15.18 (12.46) 23.37 (39.61) 28.29 (37.27) 21.96 (31.99)

25.73 (19.36) 37.00 (32.36) 35.29 (24.77) 32.77 (25.41)

17.59 (12.03) 34.32 (38.68) 23.21 (13.50) 25.52 (26.43)

0.49 0.59 0.69 0.60

(0.29) (0.19) (0.14) (0.22)

0.48 0.65 0.69 0.59

(0.29) (0.19) (0.11) (0.24)

0.34 (0.23) 0.54 (0.20) 0.62 (0.17) 0.51 (0.23)

0.55 (0.24) 0.59 (0.20) 0.69 (0.11) 0.60 (0.20)

0.34 (0.19) 0.45 (0.20) 0.58 (0.14) 0.47 (0.20)

0.47 (0.20) 0.54 (0.23) 0.65 (0.12) 0.54 (0.21)

0.50 0.65 0.60 0.58

(1.10) (0.93) (0.68) (0.89)

0.88 0.80 0.81 0.83

(1.07) (0.95) (0.98) (0.99)

0.38 (0.62) 0.35 (0.61) 0.50 (0.51) 0.42 (0.57)

0.83 (0.82) 0.55 (0.69) 0.88 (0.96) 0.75 (0.82)

0.25 (0.45) 0.29 (0.59) 0.30 (0.57) 0.28 (0.53)

0.71 (1.04) 0.70 (0.80) 0.44 (0.63) 0.63 (0.86)

*Means and standard deviations for pain threshold are based on a sample of 85 children (n = 28, 8- to 9-year-olds; n = 29, 10- to 11-year-olds; n = 28, 12- to 14-year-olds). Twentyeight children were excluded as they did not indicate their pain threshold during one or more of the CPT immersions. Means and standard deviations for worst and average pain intensity, pain tolerance, pain unpleasantness, and pain-related fear are based on the full sample of 113 children (n = 40, 8- to 9-year-olds; n = 37, 10- to 11-year-olds, n = 36, 12- to 14-year-olds).

group, F(2, 107) = 4.68, P < 0.05. Planned pairwise comparisons indicated that 12- to 14-year-olds rated their worst pain intensity significantly higher than 8- to 9-year-olds. Mean worst pain intensity of 10- to 11-year-olds fell between the other age groups and was not significantly different from either. No significant main effect of type of CPT apparatus was observed, F(1, 107) = 0.75, P = 0.39. Average Pain. Similar to worst pain intensity, a significant main effect of water temperature, F(2, 214) = 27.95, P < 0.01 was seen for average pain intensity ratings. However, planned pairwise comparisons revealed that average pain intensity was significantly higher at 5 and 7°C as compared to 10°C, but were not significantly different from one another. No significant main effect of age group, F(2,107) = 1.86, P = 0.16, or type of CPT apparatus, F(1, 107) = 0.58, P = 0.45 on average pain intensity ratings was observed.

Pain Tolerance Analyses revealed a significant main effect of water temperature, F(2, 214) = 24.50, P < 0.01 on pain tolerance. Planned pairwise comparisons revealed that pain tolerance was significantly lower at 5°C than at 7°C and 10°C, and significantly lower at 7°C as compared to 10°C. This indicates that as water temperature decreased, pain tolerance decreased. There was also a significant main effect of age group, F(2, 107) = 4.79, P < 0.01. Planned pairwise comparisons indicated that 12- to 14-year-olds had significantly greater pain tolerance than 8- to 9-year-olds. However, a significant interaction was noted between water temperature and age group on pain tolerance, F(4, 214) = 3.29, P < 0.05, indicating that children of different ages were differentially impacted by water temperature. Simple main effects tests revealed that 10- to 11-year-olds had significantly greater pain tolerance than 8- to 9-yearolds at 10°C only, but were not significantly different

BIRNIE ET AL.

than 12- to 14-year-olds. At 5°C than at 7°C, mean pain tolerance of 10- to 11-year-olds fell between the other age groups and was not significantly different from either. No significant main effect of type of CPT apparatus was observed, F(1, 107) = 1.96, P = 0.17. See Figures 2 and 3 for survival curves for pain tolerance (ie, proportion of children with hand immersed in the cold pressor by tolerance time) separated by water temperature (Figure 2) and child age group (Figure 3).

1.0 Proportion of Participants with Hand Immersed

52 

8-9 year olds 10-11 year olds 12-14 year olds

0.8

0.6

0.4

0.2

Pain Threshold 0.0

Analyses revealed a significant main effect of water temperature, F(2, 158) = 12.43, P < 0.01, on pain threshold. Planned pairwise comparisons revealed that pain threshold was significantly greater at 10°C as compared to 5°C and 7°C, which were not significantly different from one another. No significant main effect of age group, F(2, 79) = 1.96, P = 0.19, or type of CPT apparatus, F(1, 79) = 0.37, P = 0.54, on pain threshold was observed. Pain Unpleasantness Analyses revealed a significant main effect of water temperature, F(2, 214) = 13.53, P < 0.01, on pain unpleasantness. Planned pairwise comparisons revealed that pain unpleasantness was significantly greater at 5 and 7°C as compared to 10°C, indicating that colder water was more unpleasant; 5 and 7°C were not

Proportion of Participants with Hand Immersed

1.0

5 degrees 7 degrees 10 degrees

0

20 40 60 80 100 120 140 160 180 200 220 240 Pain Tolerance (seconds)

Figure 3. Pain tolerance survival curves by child age group.

significantly different from one another. There was also a significant main effect of age, F(2, 107) = 14.13, P < 0.01. Planned pairwise comparisons indicated that 8- to 9-year-olds had significantly lower pain unpleasantness than both 10- to 11-year-olds and 12- to 14-year-olds; 10- to 11-year-olds had significantly lower pain unpleasantness than 12- to 14-year-olds. A significant main effect of type of CPT apparatus was also observed, F(1, 107) = 5.62, P < 0.05, with pain induced by the electric-cooled cold pressor reported as significantly more unpleasant overall. However, a significant interaction was noted between water temperature and type of CPT apparatus, F(4, 214) = 4.10, P < 0.05. Simple main effects indicated that the electric-cooled cold pressor was significantly more unpleasant at 7 and 10°C only with no differences at 5°C. Pain-related Fear

0.8

Analyses revealed a significant main effect of type of CPT apparatus, F(1, 106) = 6.52, P < 0.05, with painrelated fear during the electric-cooled cold pressor rated significantly higher than during the ice-cooled cold pressor. No significant main effect of water temperature, F(2, 212) = 0.16, P = 0.85, or age group, F(2, 106) = 0.03, P = 0.97, on pain-related fear was observed.

0.6

0.4

0.2

0.0 0

20 40 60 80 100 120 140 160 180 200 220 240 Pain Tolerance (seconds)

Figure 2. Pain tolerance survival curves by water temperature.

Sex Differences Girls had significantly longer pain tolerance as compared with boys at 5°C (t = 3.53, P < 0.01), 7°C

CPT Temperature, Apparatus, and Child Age  53

(t = 3.41, P < 0.01), and 10°C (t = 3.79, P < 0.01). Girls also had significantly greater pain threshold than boys at 5°C (t = 3.02, P < 0.01), 7°C (t = 2.11, P < 0.05), and 10°C (t = 3.23, P < 0.01). No differences were observed between boys and girls for worst and average pain intensity, pain unpleasantness, or painrelated fear at any temperature.

Children’s Identification of Water Temperature and Spontaneous Coping Children were better than chance at identifying the coldest and warmest of the three CPT immersions they had experienced. Seventy-two children (63.7%) correctly identified which CPT was the coldest and 74 children (65.5%) correctly identified which CPT was the warmest. Children’s spontaneous coping during the CPT was coded from responses to the question asking whether they did anything to help keep their hand in the water longer. The majority of children reported distracting themselves (n = 36, 31.9%), followed by moving their hand/fingers (n = 29, 25.7%), doing nothing (n = 29, 25.7%), positive self-talk (eg, “thinking I can do this”; n = 8, 8.0%), and other (eg, “tried not to feel anything”; n = 10, 8.8%).

DISCUSSION This study investigated the impact of three water temperatures (5, 7, and 10°C), two types of apparatus (ice- vs. electric-cooled), and child age (8 to 9 years, 10 to –11 years, 12 to 14 years), on pain-related outcomes during the CPT in a sample of 113 healthy children. These variables were assessed given their known inconsistency in pediatric CPT studies7 and posited impact on pain responding during the CPT in both adults and children.6,8,14,15,30 Consistent with hypotheses and previous research,6,14,31 small differences in water temperature had a notable impact on pain outcomes. Specifically, 2 and 3°C decreases in water temperature led to significantly increased worst pain and shorter pain tolerance; 3 and 5°C decreases in water temperature led to significantly increased average pain and pain unpleasantness, and decreased pain threshold. That is, significant differences were noted for these latter findings when 5 and 7°C were compared with 10°C, but not compared with one another. Changes in water temperature had no impact on pain-related fear.

This study is the first to demonstrate the impact of CPT water temperature in children and extends research with adults by demonstrating that even smaller changes in water temperature ( 2°C) significantly influences pain tolerance and pain unpleasantness.14,31 It also contradicts recent research with adults, which showed no impact of water temperature on pain threshold during the cold pressor.15 These discrepant findings may be explained by the inclusion of a warmer temperature in the present study (ie, 10°C), as pain thresholds at the cooler temperatures (5 and 7°C) were not significantly different from one another. However, an important strength of the present study is the use of a within subjects design with all individuals exposed to all three temperatures. The lack of a significant impact of water temperature on pain threshold by Koenig and colleagues15 might be accounted for by differences between groups. Despite randomizing water temperature order and returning the hand to baseline temperature between CPT immersions, children’s accuracy in identifying the coldest and warmest immersions suggests that even a few degree difference in water temperature is perceptible. Although detection thresholds are worse for temperatures below 10°C,16 our findings are consistent with research indicating that children detect less than 2 to 3°C changes in cold stimuli.32 Average skin temperature after removal of the hand from CPT immersions at all three temperatures (18.71 to 20.02°C) was comparable to cold pain thresholds in children aged 6 to 16 years during quantitative sensory testing (16.27 to 22.43°C),32 as well as skin temperature of adults after a 3-minute CPT immersion at 2°C (17.2°C).5 Pain tolerance survival curves at 10°C are comparable to previous work with approximately 50% of children removing their hand by 1 minute.30 Our findings extend this work by showing that closer to 60% of children at 7°C and 70% at 5°C reach pain tolerance by 1 minute. Furthermore, that tolerance survival curves are also highly dependent on child age and the significant interaction between water temperature and child age. This finding has important implications for comparisons across studies as some CPT researchers have examined pain tolerance by comparing children who reach preset maximum immersion times to those who do not.33 Given that the proportion of children reaching those ceilings depends on water temperature and child age, CPT methodology could lead to differences between studies.

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Significant differences in pain outcomes overall were also observed based on child age, particularly between the youngest (8 to 9 year old) and oldest (12 to 14 year old) groups. Surprisingly, the oldest children reported significantly higher pain intensity and unpleasantness as compared to the youngest children, although this is likely due to their longer-lasting pain experience as revealed through significantly longer pain tolerance times. Pain outcomes in the 10- to 11-year-olds largely fell between the extreme age groups and were generally not significantly different from either, with the exception of pain unpleasantness and pain tolerance (at 10°C only). Coupled with a recent study that reported longer pain tolerance and threshold for older children,12 our findings suggest that age effects may have been washed out in a previous study reporting minimal age differences in CPT outcomes comparing children 10 years and older to those under 10.30 Given the impact of child age on certain pain outcomes, researchers should consider differences in age ranges of children when comparing findings across studies. Consistent with other experimental pain, child age had no impact on cold pain threshold32,34 or average pain intensity. Type of CPT apparatus had more minimal impact on pain outcomes, with the electric-cooled apparatus associated with increased pain-related fear, as well as increased pain unpleasantness at 7 and 10°C only. Type of CPT apparatus had no impact on pain intensity, tolerance, or threshold. Children’s pre-CPT state anxiety was not impacted by type of CPT apparatus, suggesting that differences in appearance between the two CPT apparatus did not influence how anxious children were before the CPT. One possible mechanism contributing to significant differences in pain outcomes between the types of apparatus is the amount and circulation rate of the cold water.8 The ice-cooled apparatus uses more water and a slower circulation rate (24 L circulated at 3.33 L/minute) than the ice-cooled apparatus (8 L circulated at 10 L/minute). However, it should also be noted that both the ice- and electriccooled apparatus maintained a stable water temperature from before to after each CPT immersion and that decreased hand temperatures post-CPT immersion were not significantly different between types of apparatus. Thus, while efforts have been made to standardize type of CPT apparatus, the impact of different apparatus on comparison of findings across studies may be more limited than expected.8 Sex differences were observed for pain tolerance and threshold only, with girls reporting higher toler-

ance and threshold at all water temperatures. Unlike adults,35 the majority of pediatric CPT studies show no differences in pain outcomes based on child sex.36 Two studies have reported greater pain tolerance among girls,37,38 although one of these studies attributed observed sex differences to differences in age.37 Other noted sex differences in previous pediatric CPT studies show girls reporting significantly higher pain intensity than boys.36 Although we were underpowered in the current study to examine sex differences within the three age groups, a recent review of sex differences in children’s responding to experimental pain suggests the relevance of developmental stage.36 This warrants further inquiry in a study sufficiently powered and designed to explore inconsistencies in CPT responding based on child sex. Researchers can draw from this study’s finding when designing future CPT studies with children and adolescents. More specifically, the water temperature and/or type of CPT apparatus may depend on the nature of a particular research question and the age of children studied. For example, researchers may choose a warmer water temperature for younger samples in an effort to apply the minimal amount of stimulus necessary or alternatively may choose a colder water temperature when trying to avoid or minimize ceiling effects in pain tolerance. Researchers particularly interested in the applicability of study findings to clinical pain may choose the electric-cooled apparatus due to greater painrelated fear, which is closer to means reported during venipuncture.26 However, given the more minimal impact of type of CPT apparatus on pain outcomes, researchers should also weigh the potential benefits of electric-cooled CPT apparatus against its significantly higher cost. Studies including a wide age range of participants should be aware of and consider differential pain responding based on child age when interpreting study findings, despite consistency in study methodology. Researchers should also note children’s low levels of anxiety prior to the CPT, as has been previously reported,39 and address children’s spontaneous coping strategies in task instructions (ie, use of distraction or finger/hand movement) if relevant to particular research questions. A limitation of the study was data collection at a single research center. Previous work has demonstrated differences in pain tolerance survival curves at the same water temperature for children tested at various research centers.21 This may be due to unmeasured differences between research sites or variability in task instructions,

CPT Temperature, Apparatus, and Child Age  55

which has been shown to influence pain responding and use of coping strategies during the CPT in adults.31,40 Furthermore, while two types of CPT apparatus and water cooling were compared in this study, other types of CPT apparatus do exist21 and may vary in ways that currently have unknown impact on pain outcomes (eg, appearance, volume of water, water flow rate). Given that significant differences were found based on child age and that the CPT has been used with children as young as 3 years,20 it will be important to extend this work to a younger sample. This is highly relevant given the ethical responsibility to apply minimal stimulus, particularly in experimental pain studies, when participants have no potential for direct benefit.19 Other important research includes exploring the potential impact of other aspects of CPT methodology with known variability (eg, informed vs. uninformed ceiling, use of warm water bath).7 Furthermore, while research demonstrates unique brain activation in adults completing the CPT,5 water temperatures used with adults are typically colder than those used with children14 and at noxious cold temperatures associated with differential pain processing.17 Studies are needed that investigate potential differences in pain processing induced by the CPT at warmer water temperatures more commonly used with children and how these compare with clinical pain experiences. Regardless, this work results provide critically important information about water temperature, apparatus, and child age on CPT pain responding. Its results inform design of future CPT studies and direct consideration of methodological variability and child age when interpreting study findings.

ACKNOWLEDGEMENTS K.A. Birnie is a Vanier Canada Graduate Scholar supported by the Canadian Institutes of Health Research (CIHR). She is also a trainee member of Pain in Child Health (PICH): a CIHR Strategic Training Initiative. C.T. Chambers were supported by a Canada Research Chair, and her laboratory is funded by a Canada Foundation for Innovation grant.

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