Table 1.

Results of Published Studies (n = 14) Evaluating Pain in Children After Traumatic Brain Injury, Sorted by Method of Pain Assessment

Author, year, location	Study design	Case/ control (n)	Case severity	Source of cases	Source of controls	Age of cases (years)	Sex of cases (M/F)	Time post-injury	Pain assessment method	Findings	Level of evidencea
Pain by body region (n = 1)
Tham and colleagues, 2013, USA	Propsective cohort	144/NA	Mild to severe TBI	10 Washington study hospitals and 1 hospital in Pennsylvania	NA	M = 15.7; SD = ±1.2	100/44	3, 12, 24, 36 months	4 questions about pain in the past week (child report): 1) Numerical rating scale, 0–10 2) Pain “other than a headache that bothered you” 3) If yes, identify where (8 options) 4) Numerical rating scale of the pain intensity in the other identified area(s)	Pain prevalence did not decline over the period from 3 months to 36 months after TBI. In the persistent pain subgroup, 57.1% endorsed pain involving more than 1 anatomic region. Adolescents with persistent pain had significantly higher levels of depressive symptoms, PTSD symptomatology, and poorer HRQOL compared to the infrequent pain subgroup (p < 0.0001).	1
Overall pain rating (n = 3)
Batailler and colleagues, 2014, France	Prospective cohort	127/1283 Selected out of 1283 persons in the database, but not analyzed as a control	Mild or moderate TBI (M-AIS) attributed to a road accident	Pediatric ESPARR cohort	Rhone registry	n = 31 (age 0–5); n = 87 (age 6–11); n = 99 (age 12–16)	82/45	6 months and 1 year	Child Health Questionnaire (parents form)-50: bodily pain	Significant correlation between body pain and quality of life (r = 0.482; p < 0.001) 77.5% of children who had not fully recovered by 1 year post-injury had body pain; 10.8% had body pain in the children who did recovery completely.	1
Brown, Kenardy and Dow, 2014, Australia	Prospective cohort	195/NA	Mild to severe TBI	3 Australian hospitals	NA	M = 10.78; SD = ±2.49 (range, 6–15 years)	137/59	3, 6, 18 months	Child Health Questionnaire (parent form): bodily pain	CHQ mean pain score (standardized) was 77.23 at 3 months, 80.01 at 6 months, and 83.92 at 18 months post-TBI. Structural equation modeling supports PTSD as driving pain. PTSD predicted pain, but only in the short term.	1
McLeod, Bay and Snyder, 2010, USA	Retrospective case-control	140/126 Football athletes with concussion matched to athletes without concussion	Mild TBI	5 local high schools in Arizona	5 local high schools in Arizona	Concussion group: M = 15.0; SD = ±1.3 Control group: M = 14.6; SD = ±1.2	266 M	66.1%> 1 year, 19.1% within 1 year, 7% within the past 6 months, 6.1% within the past 3 months, and 1.4% within 1 month	Medical Outcomes Short Form-36 (child report):	The concussion group reported significantly lower mean scores/higher pain (p < 0.001) on the bodily pain (52.86 ± 6.9) compared to the control group (55.56 ± 7.3), with an effect size of 0.35.	3
Symptom questionnaire (n = 3)
Haran and colleagues, 2016, Australia	Prospective cohort	93/NA	Mild TBI	Emergency department at The Royal Children's Hospital Melbourne	NA	M = 12.7; SD = ±0.27	77/16	Not specified but average follow-up at 32 (± 5.2) days after initial ED visit	Follow-up phone call assessing post-concussive symptoms. The exact questionnaire for assessing “Concussive signs and symptoms” is not specified, but is said to be adapted from validated measures. Not specified whether child or parent report	85 children completed follow-up; 65 children experienced post-concussive symptoms; fatigue (57.6%), headache (56.5%), and neck pain (25.9%) were the top three main symptoms.	2
Heyer and colleagues, 2016, USA	Retrospective cohort	1953/NA	Mild TBI	Pediatric Sports Medicine Clinic	NA	M = 14.1; SD = ±2.09	1229/724	Median 9 days, range 1–30 days	Symptom questionnaire (includes headache and neck pain) adapted from other sources Rate severity on a scale from 0 (not present) to 6 (severe) Child report	Neck pain reported by 37.1% of the sample, with a mean score of 0.86, and a related headache probability of 0.89. Principal component analysis found strong correlations for a “cephalic” component consisting of neck pain, headache, nausea, photophobia, phonophobia, and dizziness.	2
Necajauskaite and colleagues, 2005, Europe	Retrospective case- control	102/102 Matched to other mild body injury	Mild TBI	Kaunas University of Medicine Hospital and Kaunas Red Cross Hospital	Kaunas University of Medicine Hospital and Kaunas Red Cross Hospital	M = 11; SD = ±3.1	74/28	Median = 27 months and not shorter than 1 year	Standardized questionnaire of previous (year before inquiry) and present (last month before inquiry) health status and symptoms concomitant to headaches and dizziness Parent report	6 children with mild TBI (9.4%) reported pain felt with headache in other body sites. This was higher than the control group of children with other mild body injury without head trauma (n = 4, 8%), although not significant (p > 0.05).	3
Unspecified clinical assessment (e.g., based on patient report or physical exam; n = 7)
Ellis and McDonald, 2015, Canada	Case study	1/NA	Not specified	Pan Am Clinic/Concussion Program	NA	13 years old	1 M	2 days, 2 weeks, 6 weeks, 2 months	Unclear. Patient endorsement	3 days post-injury, patient endorsed headache and neck pain. Full and painless range of motion achieved. Cleared for return to sports at 2 months. Diagnosis was coexistent sports-related concussion and cervical spinal cord injury without radiographic abnormality.	4
Kwon and Jang, 2014, Korea	Case study	1/NA	Mild TBI	Yeungnam University	NA	14 years old	1 F	Initial, 29 days, 2 months, 10 weeks	Not specified, patient report	Patient involved in car accident, began to suffer posterior neck pain and back pain radiating to the right leg. Neurological examination at 10 weeks post-injury revealed quadriparesis and memory impairment. Diffusion tensor tractography showed discontinuation of both corticoreticular pathways at the midbrain level.	4
Lim and colleagues, 2007, Ukraine	Case study	1/NA	Severe TBI	Department of Pediatric Neurosurgery, Republic Crimea Children Clinical Hospital	NA	5 years old	1 M	2 weeks	Patient history examination; clinical assessment	Patient had mandibular fractures and underwent Maxillo-mandibular surgery with a Kirschner's knitting needle. After the surgery, the patient reported throbbing generalized headache, abrupt pain on his face and jaw, which was described as a burning and stabbing sensation. Radiologic films showed that Kirschner's knitting needle mobilized from the extracranial cavity into the middle cranial cavity, resulting in iatrogenic TBI.	4
Litt, 1995, USA	Case study	1/NA	Not specified. GCS score of 5 at 17 days post-collision	Columbus State Community College	NA	16 years old	1 M	Findings approx. 17 days after the first TBI and on the same day as the second TBI	Physical examination	The patient complained of left elbow pain, dizziness, and headache with vomiting, pallor, and unresponsiveness shortly after. CT scan showed an acute right-sided subdural hematoma with a midline shift.	4
Logan and colleagues, 2001, USA	Case study	1/NA	Not specified. GCS score of 15 upon arrival at ED	University of Illinois; Carle Sports Medicine	NA	18 years old	1 M	Initial assessment, 24 h, 1 week, 12 days, 1 month post-injury	Clinical exam; patient report	12 days post-TBI, patient complained of nocturnal neck pain. Clinical exam revealed an area of tenderness beneath the left occipital protuberance. Pain increased when patient turned his head to the right. One month later, the nocturnal neck pain from the cervical ligament sprain had ceased.	4
Meoded and colleagues, 2011, USA	Retrospective cohort (n = 5)	10/NA	Mild to severe TBI	Johns Hopkins Hospital, Baltimore, Maryland	NA	M = 7.18; SD = ±4.37	4/6	Not specified	Clinical assessment on admission	A 6-year-old female with GCS = 15 presented with cervical pain. MRI showed retroclival epidural hematoma, and associated tectorial membrane disruption, and minor compression of the brainstem; 5 other patients in the cohort had “minor pain.”	4
Zaremski and colleagues, 2015, USA	Case study	1	“Concussion”	Sports Medicine Clinic	NA	17 years old	0/1	Continuous follow-up	Physical examination and patient report	Patient developed neck pain 5 weeks after concussion and showed a positive Tinel sign at the left craniocervical junction. Interventional pain management (e.g., greater occipital nerve [ON], lesser ON, and third ON block) relieved the pain, but the procedures needed to be repeated and managed long term.	4

^aLevel of evidence was assessed using “Levels of Evidence for Primary Research Question (prognostic studies)” by the Center for Evidence-Based Medicine (Oxford, UK). The scores range from 1 to 5, where a higher score indicates a weaker/lower level of evidence. Level 1 corresponds to high-quality prospective studies with sufficiently high follow-up rate (≥70%); level 2 for retrospective studies of lower quality or lesser-quality prospective studies; level 3 for case-control studies; and level 4 for case studies (Howick and colleagues, 2011). Level 5 is expert opinion, which was not encompassed by the reviewed studies.

NA, not applicable; TBI, traumatic brain injury; M-AIS, Maximum Abbreviated Injury Scale; GCS, Glasgow Coma Scale; ED, emergency department; M, mean; SD, standard deviation; M/F, male/female; approx., approximately; PTSD, post-traumatic stress disorder; HRQOL, health-related quality of life; CHQ, Child Health Questionnaire; CT, computed tomography; MRI, magnetic resonance imaging.