Toward Solving the Puzzle of Pediatric Pain
Toward Solving the Puzzle of Pediatric Pain
The development and promotion of chronic pain and pain-related disability were major topics in posters and presentations at the 24th Annual Meeting of the American Pain Society. The pediatric pain forum included a seminar on the relationship between anxiety, catastrophizing, and pain in children, and participants discussed both laboratory studies and clinical populations.
Anxiety and Catastrophizing
Jennie Tsao reported a study of responses to anxiety-related questionnaires and laboratory pain tasks in 206 healthy children, ages 8-18 years, and 206 parents. She found that children's anticipatory anxiety (rated just before the pain tasks) and distal anxiety (measured with the Child Anxiety Sensitivity Index [CASI] and the Multidimentional Anxiety Scale for Children [MASC]) were related to laboratory pain-intensity ratings but not to pain tolerance. The CASI is a measure of fear of arousal symptoms (eg, tachycardia, tachypnea, and sweating), whereas the MASC measures different types of anxiety (eg, separation anxiety, social anxiety, physical symptoms, and harm avoidance).
Dr. Tsao tested models that examined the MASC and CASI as predictors of child pain intensity either directly or through the impact on child anticipatory anxiety. She found that for cold and thermal pain tasks, the MASC score was directly related to pain intensity. The CASI predicted pain intensity for all 3 laboratory tasks (cold, heat, and pressure), but only through the impact of the stimuli on anticipatory anxiety and only in girls, not in boys. When Dr. Tsao examined the influence of parents' anxiety sensitivity or fear of their own arousal symptoms (Anxiety Sensitivity Index [ASI]) on their children's laboratory pain-intensity ratings, she found that parents' anxiety sensitivity predicted their child's anxiety sensitivity, which in turn predicted their laboratory pain intensity -- but again, only in girls. Because more than 85% of the parents were mothers, the findings indicate that the mother-daughter anxiety/sensitivity link indirectly influences girls' pain responses.
This research implies that targeting mothers' own fears of bodily symptoms of anxiety may be a pathway to reducing pain in their daughters. It is possible that girls are more sensitive to their mothers' concerns about symptoms than are boys. If so, then this transgenerational, sex-related fear of symptoms may contribute to the higher prevalence of chronic pain conditions in girls vs boys, beginning during adolescence. Dr. Tsao noted that there are little data on the pain relationship between fathers and sons or fathers and daughters, and that such studies need to be carried out before definitive conclusions can be made about mothers as a primary target for intervention to prevent pain in children.
Using the same cohort of healthy children, Cynthia Myers reported data on the role of catastrophizing as a potential contributor to the sex differences noted in pain populations. Catastrophizing includes a focus on pain, with rumination, magnification, and negative evaluation of one's ability to cope with the pain. Dr. Myers studied 242 healthy children aged 8-18 years with the Pain Coping Questionnaire and measured pain intensity and tolerance in 3 laboratory pain tasks. In this laboratory pain study, castastrophizing was not generally related to pain responses in a sex-dependent manner, that is, pain intensity rose with increasing catastrophization scores for heat and pressure tasks for both boys and girls. For the cold-pressure pain task, pain intensity increased with increasing catastrophization, but only for girls. The role of catastrophization in pain was found to be emerging in this age group, but only for cold pain was there a sex difference in the relationship between catastrophization and pain. Because catastrophization is a strong predictor of pain in adults, especially in adult women, the emergence of this relationship during childhood warrants further study. For example, as in the findings of Tsao and colleagues, do mothers who catastrophize about pain induce catastrophization in their daughters and thus increase the daughters' risk for developing chronic pain? The answers to questions like this may help prevent the development of chronic pain, especially in women.
Susmita Kashikar-Zuck presented her research on anxiety in children with chronic pain. She noted that Campo and associates (2004) reported that 79% of pediatric patients (8-15 years old) with recurrent abdominal pain seen in a primary care setting met the psychiatric criteria for an anxiety disorder. At this symposium, Dr. Kashikar-Zuck reported on 291 children and adolescents (ages 4-19 years) who experienced pain for more than 3 months duration, who she had seen in her pediatric pain clinic; 70% of participants reported pain lasting for more than 6 months. She found a small but significant relationship between pain intensity and catastrophizing, supporting the laboratory pain findings noted in Dr. Myers' study. Most importantly, she found that catastrophizing was strongly related to higher levels of disability and lower levels of pain coping efficacy.
In her analysis, after controlling for pain intensity, catastrophizing was a primary predictor of functional disability. She also reported on the role of mothers' anxiety in children with chronic pain. For example, she reported studies indicating that mothers of children with recurrent abdominal pain and mothers of children with juvenile fibromyalgia reported significantly higher levels of anxiety than mothers of pain-free children.
One question raised by these studies is whether maternal anxiety could predispose a child to using catastrophizing in response to pain. We know that catastrophizing is related to higher levels of child distress and functional disability. Can we identify children at risk and intervene early enough (with parents and children) to prevent the cycle of pain, anxiety, and disability that may lead to a prolonged course of chronic pain?
Pain in Infants
Another symposium highlighted the quandary of infant pain and its relationship to the stages of development. Simon Beggs used a series of laboratory animal studies to show that neonatal pain responses cannot be considered an immature version of adult responses.
He showed that there is different underlying structural and physiologic connectivity within the somatosensory system in the neonate. He suggested that a greater understanding of the mechanisms mediating postnatal development of this somatosensory system will allow for more effective treatment of pain in infants.
Bonnie Stevens presented data on human neonates, indicating that we have a number of measures of acute pain, but we still need ways to assess chronic pain. She also reported on some studies of pharmacologic intervention in newborns undergoing painful procedures. Two different studies of ventilated newborns undergoing tracheal suctioning found no differences in pain scores or risk outcomes in infants receiving morphine vs placebo.
She also reported on her study of standard care, pacifier with water, and pacifier with sucrose. She found that sucrose seemed to be effective only after the first 7 days of life and before the end of the first month of life. Otherwise, there was little difference in the outcomes of the 3 groups.
Dr. Anand described the findings of a series of his studies and related studies of other investigators. He reported data that suggest that morphine is not effective in young neonates and suggested that neonatal opiate receptors may not be mature enough to bind to morphine. He also showed evidence that suggests that repetitive pain may lead to cell death in areas of an infant's developing brain. He concluded that repetitive pain causes poor neurologic outcomes in premature babies; increased cell death in the immature brain; abnormal behavior during adulthood; and increased vulnerability to stress, anxiety, other psychiatric disorders.
On the other hand, describing the outcome of carrying newborns in "kangaroo pouches" and other studies, Dr. Anand concluded that loving care causes improved neurologic outcomes in ex-preterm babies, reduced cell death in the developing brain, enhanced cognitive development and less behavioral problems, and improved ability to cope with stress.
Dr. Pillai-Riddell studied the attitudes of parents vs caregivers about pain and coping of infants aged 2-18 months after viewing the same videos of the healthy infants undergoing an immunization. She found that parents, nurses, and physicians agreed that infants across all age groups can feel pain and can show behavioral indicators of pain. All 3 observer groups also agreed that, with increasing infant age, the setting and the infants' mood can affect pain, but that infants will not remember the pain. The observers attributed a higher level of pain in older babies despite the identical pain-context setup in this experiment, and a higher percentage of parents were more willing to give pain medication to older infants compared with younger infants despite the same pain procedure and setting.
Context and Pain
A third symposium on pediatric pain brought together a historian, a linguist, and a clinician to address cultural and social influences on the pain experience. Dr. Meldrum, the historian, explained the different forms of narrative research, including semistructured interviews, oral histories that are unstructured and subject-driven, ethnography, written stories, and physician-patient interactions. She described a study of children with chronic pain being carried out at University of California, Los Angeles that includes quantified written patient and parent questionnaires, in-home oral histories, and videotaped patient-physician interactions. She talked about the importance of hearing the patients' own stories of their condition and the influences that the observer, including the physician, has on the construct of the story. From the work of Maynard and Heritage, it is clear that the way in which physicians ask patients about their symptoms will influence what they are told. Dr. Meldrum talked about the importance of allowing the patient to tell his or her story as a narrative before any probing begins.
Dr. Clemente, a linguistic anthropologist, described his study of taped observations of physician, child, and parent interactions over time in a pediatric oncology clinic in Barcelona, Spain. He pointed out that oncologists gave narratives even when they did not know the answers to the patients' questions. The narratives were examples of anxiety and shaped the patients' experiences. He pointed out that narrating is more than just giving information and that it is important to encourage patients to become more active in the process of co-narrating, that is, when patients are co-narrators, they can help shape their own experiences in a more effective way than as just listeners of the physicians' narratives.
Dr. Hatchette described her study of pain self-management in adolescents. She wanted to learn about the social influences on recurrent pain experiences, with focus groups as her qualitative methodology. She determined that adolescents reduced their expression of pain when pain threatened to curtail their activities with peers. However, for unfamiliar pain or severe pain, they consulted their parents. She found that over-the-counter use of medications was common, but attitudes about taking medication were negative. Peers had negative attitudes about peers who complained of pain but didn't seem to have a "reason" for it, and that girls seemed to perceive more support from peers for expressing pain than did boys. In her focus groups on parents' impact on child pain, she found that mothers influence attitudes and behaviors about pain through verbal communication, and that they modeled pain responses and management choices (eg, when to see the doctor or take medications).
Supported by an independent educational grant from Cephalon.
References
The development and promotion of chronic pain and pain-related disability were major topics in posters and presentations at the 24th Annual Meeting of the American Pain Society. The pediatric pain forum included a seminar on the relationship between anxiety, catastrophizing, and pain in children, and participants discussed both laboratory studies and clinical populations.
Anxiety and Catastrophizing
Jennie Tsao reported a study of responses to anxiety-related questionnaires and laboratory pain tasks in 206 healthy children, ages 8-18 years, and 206 parents. She found that children's anticipatory anxiety (rated just before the pain tasks) and distal anxiety (measured with the Child Anxiety Sensitivity Index [CASI] and the Multidimentional Anxiety Scale for Children [MASC]) were related to laboratory pain-intensity ratings but not to pain tolerance. The CASI is a measure of fear of arousal symptoms (eg, tachycardia, tachypnea, and sweating), whereas the MASC measures different types of anxiety (eg, separation anxiety, social anxiety, physical symptoms, and harm avoidance).
Dr. Tsao tested models that examined the MASC and CASI as predictors of child pain intensity either directly or through the impact on child anticipatory anxiety. She found that for cold and thermal pain tasks, the MASC score was directly related to pain intensity. The CASI predicted pain intensity for all 3 laboratory tasks (cold, heat, and pressure), but only through the impact of the stimuli on anticipatory anxiety and only in girls, not in boys. When Dr. Tsao examined the influence of parents' anxiety sensitivity or fear of their own arousal symptoms (Anxiety Sensitivity Index [ASI]) on their children's laboratory pain-intensity ratings, she found that parents' anxiety sensitivity predicted their child's anxiety sensitivity, which in turn predicted their laboratory pain intensity -- but again, only in girls. Because more than 85% of the parents were mothers, the findings indicate that the mother-daughter anxiety/sensitivity link indirectly influences girls' pain responses.
This research implies that targeting mothers' own fears of bodily symptoms of anxiety may be a pathway to reducing pain in their daughters. It is possible that girls are more sensitive to their mothers' concerns about symptoms than are boys. If so, then this transgenerational, sex-related fear of symptoms may contribute to the higher prevalence of chronic pain conditions in girls vs boys, beginning during adolescence. Dr. Tsao noted that there are little data on the pain relationship between fathers and sons or fathers and daughters, and that such studies need to be carried out before definitive conclusions can be made about mothers as a primary target for intervention to prevent pain in children.
Using the same cohort of healthy children, Cynthia Myers reported data on the role of catastrophizing as a potential contributor to the sex differences noted in pain populations. Catastrophizing includes a focus on pain, with rumination, magnification, and negative evaluation of one's ability to cope with the pain. Dr. Myers studied 242 healthy children aged 8-18 years with the Pain Coping Questionnaire and measured pain intensity and tolerance in 3 laboratory pain tasks. In this laboratory pain study, castastrophizing was not generally related to pain responses in a sex-dependent manner, that is, pain intensity rose with increasing catastrophization scores for heat and pressure tasks for both boys and girls. For the cold-pressure pain task, pain intensity increased with increasing catastrophization, but only for girls. The role of catastrophization in pain was found to be emerging in this age group, but only for cold pain was there a sex difference in the relationship between catastrophization and pain. Because catastrophization is a strong predictor of pain in adults, especially in adult women, the emergence of this relationship during childhood warrants further study. For example, as in the findings of Tsao and colleagues, do mothers who catastrophize about pain induce catastrophization in their daughters and thus increase the daughters' risk for developing chronic pain? The answers to questions like this may help prevent the development of chronic pain, especially in women.
Susmita Kashikar-Zuck presented her research on anxiety in children with chronic pain. She noted that Campo and associates (2004) reported that 79% of pediatric patients (8-15 years old) with recurrent abdominal pain seen in a primary care setting met the psychiatric criteria for an anxiety disorder. At this symposium, Dr. Kashikar-Zuck reported on 291 children and adolescents (ages 4-19 years) who experienced pain for more than 3 months duration, who she had seen in her pediatric pain clinic; 70% of participants reported pain lasting for more than 6 months. She found a small but significant relationship between pain intensity and catastrophizing, supporting the laboratory pain findings noted in Dr. Myers' study. Most importantly, she found that catastrophizing was strongly related to higher levels of disability and lower levels of pain coping efficacy.
In her analysis, after controlling for pain intensity, catastrophizing was a primary predictor of functional disability. She also reported on the role of mothers' anxiety in children with chronic pain. For example, she reported studies indicating that mothers of children with recurrent abdominal pain and mothers of children with juvenile fibromyalgia reported significantly higher levels of anxiety than mothers of pain-free children.
One question raised by these studies is whether maternal anxiety could predispose a child to using catastrophizing in response to pain. We know that catastrophizing is related to higher levels of child distress and functional disability. Can we identify children at risk and intervene early enough (with parents and children) to prevent the cycle of pain, anxiety, and disability that may lead to a prolonged course of chronic pain?
Pain in Infants
Another symposium highlighted the quandary of infant pain and its relationship to the stages of development. Simon Beggs used a series of laboratory animal studies to show that neonatal pain responses cannot be considered an immature version of adult responses.
He showed that there is different underlying structural and physiologic connectivity within the somatosensory system in the neonate. He suggested that a greater understanding of the mechanisms mediating postnatal development of this somatosensory system will allow for more effective treatment of pain in infants.
Bonnie Stevens presented data on human neonates, indicating that we have a number of measures of acute pain, but we still need ways to assess chronic pain. She also reported on some studies of pharmacologic intervention in newborns undergoing painful procedures. Two different studies of ventilated newborns undergoing tracheal suctioning found no differences in pain scores or risk outcomes in infants receiving morphine vs placebo.
She also reported on her study of standard care, pacifier with water, and pacifier with sucrose. She found that sucrose seemed to be effective only after the first 7 days of life and before the end of the first month of life. Otherwise, there was little difference in the outcomes of the 3 groups.
Dr. Anand described the findings of a series of his studies and related studies of other investigators. He reported data that suggest that morphine is not effective in young neonates and suggested that neonatal opiate receptors may not be mature enough to bind to morphine. He also showed evidence that suggests that repetitive pain may lead to cell death in areas of an infant's developing brain. He concluded that repetitive pain causes poor neurologic outcomes in premature babies; increased cell death in the immature brain; abnormal behavior during adulthood; and increased vulnerability to stress, anxiety, other psychiatric disorders.
On the other hand, describing the outcome of carrying newborns in "kangaroo pouches" and other studies, Dr. Anand concluded that loving care causes improved neurologic outcomes in ex-preterm babies, reduced cell death in the developing brain, enhanced cognitive development and less behavioral problems, and improved ability to cope with stress.
Dr. Pillai-Riddell studied the attitudes of parents vs caregivers about pain and coping of infants aged 2-18 months after viewing the same videos of the healthy infants undergoing an immunization. She found that parents, nurses, and physicians agreed that infants across all age groups can feel pain and can show behavioral indicators of pain. All 3 observer groups also agreed that, with increasing infant age, the setting and the infants' mood can affect pain, but that infants will not remember the pain. The observers attributed a higher level of pain in older babies despite the identical pain-context setup in this experiment, and a higher percentage of parents were more willing to give pain medication to older infants compared with younger infants despite the same pain procedure and setting.
Context and Pain
A third symposium on pediatric pain brought together a historian, a linguist, and a clinician to address cultural and social influences on the pain experience. Dr. Meldrum, the historian, explained the different forms of narrative research, including semistructured interviews, oral histories that are unstructured and subject-driven, ethnography, written stories, and physician-patient interactions. She described a study of children with chronic pain being carried out at University of California, Los Angeles that includes quantified written patient and parent questionnaires, in-home oral histories, and videotaped patient-physician interactions. She talked about the importance of hearing the patients' own stories of their condition and the influences that the observer, including the physician, has on the construct of the story. From the work of Maynard and Heritage, it is clear that the way in which physicians ask patients about their symptoms will influence what they are told. Dr. Meldrum talked about the importance of allowing the patient to tell his or her story as a narrative before any probing begins.
Dr. Clemente, a linguistic anthropologist, described his study of taped observations of physician, child, and parent interactions over time in a pediatric oncology clinic in Barcelona, Spain. He pointed out that oncologists gave narratives even when they did not know the answers to the patients' questions. The narratives were examples of anxiety and shaped the patients' experiences. He pointed out that narrating is more than just giving information and that it is important to encourage patients to become more active in the process of co-narrating, that is, when patients are co-narrators, they can help shape their own experiences in a more effective way than as just listeners of the physicians' narratives.
Dr. Hatchette described her study of pain self-management in adolescents. She wanted to learn about the social influences on recurrent pain experiences, with focus groups as her qualitative methodology. She determined that adolescents reduced their expression of pain when pain threatened to curtail their activities with peers. However, for unfamiliar pain or severe pain, they consulted their parents. She found that over-the-counter use of medications was common, but attitudes about taking medication were negative. Peers had negative attitudes about peers who complained of pain but didn't seem to have a "reason" for it, and that girls seemed to perceive more support from peers for expressing pain than did boys. In her focus groups on parents' impact on child pain, she found that mothers influence attitudes and behaviors about pain through verbal communication, and that they modeled pain responses and management choices (eg, when to see the doctor or take medications).
Supported by an independent educational grant from Cephalon.
References
Zeltzer L, Tsao JCI, Myers CD, Kashikar-Zuck S. Anxiety and catastrophization in children's laboratory and non-laboratory pain populations. Focus group discussion. Pediatric pain forum, Wednesday, March 30, 2005. Program and abstracts of the 24th Annual Scientific Meeting of the American Pain Society; March 30-April 2, 2005; Boston, Massachusetts.
Tsao J, Lu Q, Turk N, et al. Structural equation modeling of the relationships among parent and child anxiety sensitivity and child laboratory pain. J Pain. 2005;815:S62.
Tsao JC, Myers CD, Craske MG, et al. Role of anticipatory anxiety and anxiety sensitivity in children's and adolescents' laboratory pain responses. J Pediatr Psychol. 2004;29:379-388. Abstract
Reid GJ, Gilbert CA, McGrath PJ. The Pain Coping Questionnaire: preliminary validation. Pain. 1998;76:83-96. Abstract
Campo JV, Bridge J, Ehmann M, et al. Recurrent abdominal pain, anxiety, and depression in primary care. Pediatrics. 2004;113:817-824. Abstract
Kashikar-Zuck S, Vaught MH, Goldschneider KR, Graham TB, Miller JC. Depression, coping, and functional disability in juvenile primary fibromyalgia syndrome. J Pain. 2002;3:412-419. Abstract
Kashikar-Zuck S, Goldschneider KR, Powers SW, et al. Depression and functional disability in chronic pediatric pain. Clin J Pain. 2001;17:341-349. Abstract
Walker LS, Greene JW. Children with recurrent abdominal pain and their parents: more somatic complaints, anxiety, and depression than other patient families? J Pediatr Psychol. 1989;14:231-243.
Pillai-Riddell R, Stevens B, Beggs S, Anand K. Infant pain: sharpening our understanding within critical stages of infant development. Symposium 308, Friday, April 1, 2005. Program and abstracts of the 24th Annual Scientific Meeting of the American Pain Society; March 30-April 2, 2005; Boston, Massachusetts.
Fitzgerald M, Beggs S. The neurobiology of pain: developmental aspects. Neuroscientist. 2001;7:246-57. Abstract
Stevens B, Gibbins S. Clinical utility and clinical significance in the assessment and management of pain in vulnerable infants. Clin Perinatol. 2002;29:459-468. Abstract
Anand KJ, Hall RW, Desai N, et al; NEOPAIN Trial Investigators Group. Effects of morphine analgesia in ventilated preterm neonates: primary outcomes from the NEOPAIN randomised trial. Lancet. 2004 May 22;363(9422):1673-1682.
Liu JG, Rovnaghi CR, Garg S, Anand KJ. Opioid receptor desensitization contributes to thermal hyperalgesia in infant rats. Eur J Pharmacol. 2004 May 3;491(2-3):127-136.
Simons SH, van Dijk M, van Lingen RA, et al. Routine morphine infusion in preterm newborns who received ventilatory support: a randomized controlled trial. JAMA. 2003 Nov 12;290(18):2419-2427.
Simons SH, van Dijk M, Anand KS, et al. Do we still hurt newborn babies? A prospective study of procedural pain and analgesia in neonates. Arch Pediatr Adolesc Med. 2003 Nov;157(11):1058-1064.
Stevens B, Yamada J, Ohlsson A. Sucrose for analgesia in newborn infants undergoing painful procedures. Cochrane Database Syst Rev. 2004;(3):CD001069.
Gibbins S, Stevens B, Hodnett E, et al. Efficacy and safety of sucrose for procedural pain relief in preterm and term neonates. Nurs Res. 2002;51:375-382. Abstract
Soriano SG, Anand KJ, Rovnaghi CR, Hickey PR. Of mice and men: should we extrapolate rodent experimental data to the care of human neonates? Anesthesiology. 2005;102:866-868.
Peters JW, Schouw R, Anand KJ, et al. Does neonatal surgery lead to increased pain sensitivity in later childhood? Pain. 2005;114:444-454.
Tibboel D, Anand KJ, van den Anker JN. The pharmacological treatment of neonatal pain. Semin Fetal Neonatal Med. 2005;10:195-205. Abstract
Anand KJ, Jacobson B, Hall RW. Gastric suction at birth: not an innocent bystander. J Pediatr. 2004;145:714.
Pillai-Riddell RR, Badali MA, Craig KD. Parental judgments of infant pain: importance of perceived cognitive abilities, behavioural cues and contextual cues. Pain Res Manag. 2004;9:73-80. Abstract
Zeltzer LK, Hatchette J, Clemente I, Meldrum ML. Cross-cultural narratives in pediatric pain research and therapy. Symposium 321. Saturday, April 2, 2005. Program and abstracts of the 24th Annual Scientific Meeting of the American Pain Society; March 30-April 2, 2005; Boston, Massachusetts.
Maynard DW, Heritage J. Conversation analysis, doctor-patient interaction and medical communication. Med Educ. 2005;39:428-435. Abstract
Meldrum ML. A capsule history of pain management. JAMA. 2003;290:2470-2475. Abstract
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