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Current Status of Pain Management
in Children
Richard F. Howard, MB, FRCA
Many changes have taken place in pediatric pain management since the
MORETHAN25YEARSHAVE undertreatmentofchildren’spainwasfirstreported.Notableadvancesin-
clude an increase in understanding pain during development and improve-
ments in the management of acute pain. Although much more about the safe
and effective management of pain in children is now known, this knowl-
ment of children’s pain.1,2 Since then, edge has not been widely or effectively translated into routine clinical prac-
tice. Lack of suitable research on which to firmly establish evidence-based
care is likely to have contributed to this situation. A subject of considerable
tially in need of analgesia, improve-ments in the quality of pain treatment interest recently is the discovery that the experience of pain in early life may
lead to long-term consequences. New research findings from laboratory and
clinical studies have clearly identified possible mechanisms and provided
evidence that long-term behavioral changes can extend far beyond what would
be considered the normal period of postinjury recovery. Timing, degree of
injury, and administered analgesia and its nature may be important deter-
minants of the long-term outcome of infant pain. Chronic pain, including
known about the safe and effectivemanagement of pain in infants and neuropathic pain, is far more common in children than was thought. The as-
sessment and treatment of this pain and its functional consequences pre-
sent a considerable unmet challenge. There is a pressing need for further
research and clinical development in the management of pain in children.
surement for all children who are poten-tially in pain, application of effectiveup-to-date treatments, and improved term effects of pain and analgesia remain included pediatric, neonatal, infant pain, acute, chronic, procedural, treat- ment, nociception, hyperalgesia, and tive pain, and the pain of diagnostic and Author Affiliations: Anaesthesia and Pain Manage-
ment, Children Nationwide Pain Research Centre, and Department of Anaesthesia, Great Ormond Street Hos-pital for Children NHS Trust, London, England.
Corresponding Author and Reprints: Richard F.
Howard, MB, FRCA, Department of Anaesthesia, Great Ormond Street Hospital for Children NHS Trust, GreatOrmond Street, London WC1N 2JH, England (e-mail: 2464 JAMA, November 12, 2003—Vol 290, No. 18 (Reprinted)
2003 American Medical Association. All rights reserved.
The Study of Pain in Children
gree of cognitive ability are able to pro- report scales specifically designed to be domized controlled trials of children’s reflex, have properties reflecting the sen- dren as young as 4 years.19-22 These scales reflex is sensitized (eg, the threshold for sensitivity after surgery and that caused are unable to describe or rate it. Behav- Mechanisms of Pain
in Development
Pain Measurement
specific. Generally, the utility of physi- tensive body of literature about the mea- are suppressed by local anesthetics, opi- surement of pain in children has arisen.
2003 American Medical Association. All rights reserved.
(Reprinted) JAMA, November 12, 2003—Vol 290, No. 18 2465
pain is considerable at all ages, and the cols have been devised for the use of po- events is essential for effective analge- sic intervention and the discovery of new Prolonged Effects
of Early Pain Experience
low more flexibility in administering an- which is a manifestation of profound dif- become routine; topical preparations (li- cesses of central and peripheral sensiti- perioperative pain.57,58 Early studies of cardiovascular safety and efficacy of the jor surgery in the neonatal period, in this gesia, had little effect on subsequent pain gery, but its place in the practice of pe- nociceptive responses at different stages ity is a particular concern.61 Agents new tissue injury is superficially similar to that of the adult but differs in onset, pat- cal sensitivity for some time after heal- systemically and epidurally.62-64 The ap- dependent, opioid analgesic effects.40,41 cognitive-behavioral strategies: distrac- but not all, of these effects appear to be trained practitioners. Intuitively, these unclear, so further study is required.
states at all ages, and the effects of this Acute Pain
ologic responses to acute pain.68-70 They 2466 JAMA, November 12, 2003—Vol 290, No. 18 (Reprinted)
2003 American Medical Association. All rights reserved.
tive or negative long-term effects on the the means to answer these questions.
surgery is prevalent.10,72,73 Pain assess- ment skills and are from a number of dis- treatment and serve as practical and edu- Chronic Pain
Chronic or recurrent pain affects a large appropriate help or treatment.11,76-78 The with juvenile rheumatoid arthritis, sickle function, are needed to assess the clini- ity of life, in addition to control of pain later life. Little is known of its mecha- Future Research and
Developments
also increasingly diagnosed, as are other further clinical development in the field so-called idiopathic pain syndromes.
of infant pain has been little studied in but a significant proportion go on to de- care standards, are likely also to lead to disability that are difficult to treat.84,85 tine practice.97 Such initiatives may also effort will be required to redress this im- ports started to appear in the 1980s, and portant clinical issues yet to be resolved.
2003 American Medical Association. All rights reserved.
(Reprinted) JAMA, November 12, 2003—Vol 290, No. 18 2467
17. IASP Subcommittee on Taxonomy. Pain terms: a
37. Page GG, Blakely WP, Ben-Eliyahu S. Evidence that
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2003 American Medical Association. All rights reserved.
(Reprinted) JAMA, November 12, 2003—Vol 290, No. 18 2469
tivity. On the other hand, glucocorticoids have a direct inhibi- lation analysis did not show any correlation between tory effect on adiponectin secretion and expression.6 Simi- adipocytokines and concomitant medication. In addition, none larly, resistin concentration is known to increase in response of the patients with RA were receiving TNF-␣ inhibitors.
to glucocorticoids and to decrease in response to TNF-␣.7 The We disagree with the suggestion of Stefan et al that our study complex nature of these various mechanisms could be clari- found a nonnegative association between BMI and either adi- fied by studying patients with RA who had not been treated ponectin or resistin. As expected, patients with OA had sig- nificantly higher BMI than patients with RA. However, as men- The authors also reported that adiponectin levels in syno- tioned in our article, partial correlation analysis revealed vial fluid were positively, although not quite significantly, re- nonsignificant correlations between BMI and concentrations lated to body mass index (BMI). If synovial concentrations of of adiponectin (r=0.246, P=.08) and resistin (r=0.245, P=.07).
adiponectins reflect plasma concentrations, then this is a sur- We also doubt their speculation that serum levels reflect sy- prising finding, as there appears to be a strong negative corre- novial fluid levels of inflammatory arthritides such as RA. There lation between plasma adiponectin concentrations and mea- is no evidence in the literature for an “overspill” phenomenon sures of obesity.3 Moreover, plasma adiponectin concentrations between serum and synovial adipocytokines. In contrast, among are substantially lower in men than in women, necessitating patients with RA, synovial concentrations of numerous cyto- further adjustment for sex. The lower degree of adiposity among kines are clearly elevated compared with serum.1 Our ongo- patients with RA may therefore represent an alternative expla- ing studies2 have found that both adiponectin mRNA and pro- nation for the higher synovial adiponectin concentrations in tein are strongly expressed not only in synovial adipocytes but also in activated synovial fibroblasts. Therefore, the absence Norbert Stefan, MD
of any correlation between synovial fluid adipocytokines and [email protected]
BMI is not unexpected, as synovial adipocytokines are prob- Hans-Ulrich Ha¨ring, MD
ably produced locally, perhaps from activated synovial cells, Michael Stumvoll, MD
rather than systemically from body fat stores. Our data sug- Department of Internal Medicine
gest that the increased levels of adipocytokines in synovial fluid University of Tu¨bingen
in patients with active RA are largely derived from activated Tu¨bingen, Germany
1. Scha¨ffler A, Ehling A, Neumann E, et al. Adipocytokines in synovial fluid. JAMA.
2003;290:1709-1710.
Andreas Scha¨ffler, MD
2. Krakoff J, Funahashi T, Stehouwer CD, et al. Inflammatory markers, adiponec-
Ulf Mu¨ller-Ladner, MD
tin, and risk of type 2 diabetes in the Pima Indian. Diabetes Care. 2003;26:1745- Department of Internal Medicine I
University of Regensburg
3. Chandran M, Phillips SA, Ciaraldi T, Henry RR. Adiponectin: more than just an-
other fat cell hormone? Diabetes Care. 2003;26:2442-2450.
Regensburg, Germany
4. Ouchi N, Kihara S, Arita Y, et al. Adiponectin, an adipocyte-derived plasma pro-
tein, inhibits endothelial NF-kappaB signaling through a cAMP-dependent path- di Giovine FS, Poole S, Situnayake RD, Wadhwa M, Duff GW. Absence of cor- relations between indices of systemic inflammation and synovial fluid interleu- Circulation. 2000;102:1296-1301.
5. Maeda N, Takahashi M, Funahashi T, et al. PPARgamma ligands increase ex-
kin-1 (alpha and beta) in rheumatic diseases. Rheumatol Int. 1990;9:259-264.
2.
pression and plasma concentrations of adiponectin, an adipose-derived protein.
Ehling A, Scha¨ffler A, Grifka J, et al. Modulation of cytokine and MMP syn- thesis of synovial fibroblasts by adipocytokine adiponectin and adipocytes. Arthri- 6. Halleux CM, Takahashi M, Delporte ML, et al. Secretion of adiponectin and
regulation of apM1 gene expression in human visceral adipose tissue. Biochem
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sion in 3T3-L1 and mouse adipose cells. Diabetes. 2002;51:1737-1744.
CORRECTION
In Reply: Dr Stefan and colleagues suggest that corticoste-
Incorrect Insertion: In the Special Communication entitled “Current Status of Pain
roids might influence the levels of adipocytokines. Although Management in Children” published in the November 12, 2003, issue of THE JOUR- this is a possibility, none of our patients with OA were receiv- NAL (2003;290:2464-2469), incorrect wording was inserted during the editing stage.
ing corticosteroids or other immunosuppressive therapy. Fur- On page 2466 in the second paragraph under “Prolonged Effects of Early PainExperience,” the third sentence should not begin with the words “In humans” thermore, in the subgroup of patients with RA, partial corre- because the paragraph is discussing laboratory studies in animal models.
2004 American Medical Association. All rights reserved.
(Reprinted) JAMA, February 11, 2004—Vol 291, No. 6 695

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