Christine M. Dengler-Crish

Functional abdominal pain in childhood and adolescence increases risk for chronic pain in adulthood

&NA; A few studies of long‐term outcomes for pediatric functional abdominal pain (FAP) have assessed acute non‐abdominal pain at follow‐up, but none has assessed chronic pain. We followed a cohort of pediatric patients with FAP (n = 155) and a well control group (n = 45) prospectively for up to 15 years. Participants ranged in age from 18 to 32 years at a follow‐up telephone interview. FAP patients were classified as Resolved (n = 101) versus Unresolved (n = 54) at follow‐up, based on whether they reported symptoms consistent with the adult Rome III criteria for a functional gastrointestinal disorder. Headache symptoms and reports of chronic non‐abdominal pain also were assessed at follow‐up. In the Unresolved group, 48.1% reported one or more sites of chronic non‐abdominal pain at follow‐up, compared to 24.7% in the Resolved group and 13.3% in the control group, p < 0.01. More than half (57.4%) of the Unresolved group endorsed symptoms consistent with International Headache Society criteria for headache, compared to 44.6% of the Resolved group and 31% of controls, p < 0.05. One‐third of the Unresolved group reported both headache and one or more sites of chronic non‐abdominal pain at follow‐up, compared to 17.8% of the Resolved group and 4.4% of controls. Youth with FAP that persists into adulthood may be at increased risk for chronic pain and headache. Examination of central mechanisms that are common across chronic pain disorders may enhance understanding of this subgroup of FAP.

Somatic Complaints in Childhood Functional Abdominal Pain Are Associated With Functional Gastrointestinal Disorders in Adolescence and Adulthood

Objectives: Nongastrointestinal (non-GI) somatic complaints are common in children and adults with functional gastrointestinal disorders (FGIDs). The aim of the present study was to determine whether non-GI somatic complaints in children with functional abdominal pain (FAP) were associated with FGIDs in adolescence and young adulthood. Patients and Methods: In a prospective clinic-based study, children and adolescents (ages 8–16 years) with FAP (n = 188) and well controls (n = 61) completed a validated measure of somatic symptoms. Participants were assessed 4 to 15 years later (as older adolescents and young adults) for presence of current FGIDs as defined by the Rome III criteria. Results: Of the 188 youths with pediatric FAP, 35.6% met criteria for FGIDs at follow-up. Initial levels of non-GI somatic symptoms were significantly higher in pediatric FAP participants who subsequently met criteria for FGIDs at follow-up compared with controls and pediatric FAP participants who did not meet criteria for FGIDs at follow-up. Conclusions: The association of non-GI somatic symptoms with FAP in children may identify a group that is at risk for FGIDs later in life.

Increased wind-up to heat pain in women with a childhood history of functional abdominal pain.

&NA; Idiopathic or functional abdominal pain (FAP) is common in school‐age children and typically reflects a functional gastrointestinal disorder (FGID). FGIDs in adults have been distinguished by enhanced responses of the central nervous system to pain stimuli, known as central sensitization. This study investigated whether adolescents and young adults with a history of pediatric FAP (n = 144), compared with well control subjects (n = 78), showed enhanced central sensitization demonstrated by greater temporal summation (wind‐up) to brief, repetitive heat pulses. We also assessed the role of gender and trait anxiety in wind‐up to heat pain. Women with a history of FAP showed greater wind‐up to heat pain than men with a history of FAP (P < .05) and well control subjects of both genders (P < .05). Results were similar for FAP participants whose abdominal pain was ongoing at follow‐up and those whose pain had resolved. Although anxiety was significantly higher in the FAP group compared with control subjects (P < .01) and in women compared with men (P < .05), anxiety did not explain the increased wind‐up observed in women with a childhood history of FAP. Results suggest that women with a pediatric history of FAP may have a long‐term vulnerability to pain associated with enhanced central nervous system responses to pain stimuli. Young women with a childhood history of functional abdominal pain may have a long‐term vulnerability to pain that is associated with enhanced responses of the central nervous system to pain stimuli.

Hypoalgesia Related to Elevated Resting Blood Pressure is Absent in Adolescents and Young Adults with a History of Functional Abdominal Pain

&NA; Elevated resting blood pressure (BP) is hypoalgesic in healthy individuals, but this effect is absent in adults with chronic somatic pain. This study tested whether BP‐related hypoalgesia is similarly altered in individuals with a history of chronic visceral pain in childhood. Resting BP was assessed in 94 adolescents and young adults with a known history of childhood functional abdominal pain (FAP) and 55 comparable healthy controls. Responses to an acute heat pain stimulus were then evaluated following exposure to two laboratory stressors. A significant participant type × systolic BP (SBP) interaction (p < .005) revealed that elevated resting SBP was associated with significantly higher heat pain threshold (p < .001) in healthy controls, but was unrelated to pain threshold in the FAP group. A similar pattern was observed for heat pain tolerance, with elevated SBP linked to significantly higher pain tolerance (p < .05) in healthy controls, but unrelated to tolerance in the FAP group. Dysfunction in BP‐related hypoalgesia associated with FAP was evident regardless of whether childhood FAP had resolved or still persisted at the time of laboratory testing. Subgroup analyses indicated that BP‐related hypoalgesia (in healthy controls) and FAP‐linked absence of this hypoalgesia was observed only among females. Result suggest that childhood visceral chronic pain may be associated with relatively long‐lasting dysfunction in overlapping systems modulating pain and BP that persists even after FAP resolves. Potential implications for later hypertension risk are discussed.

Growing out of a caste - reproduction and the making of the queen mole-rat

SUMMARY Naked mole-rats have a eusocial colony structure consisting of non-reproductive workers and a reproductively active caste where a single, dominant queen and 1-3 males produce all of the offspring. Well-established queens have elongated bodies that characterize their caste. Worker females retain the ability to transform into queens, however the trigger and time course for this physical transformation remain a mystery. Here, we show a direct link between periods of pregnancy and vertebral lengthening in nascent queens. Adult female mole-rats were paired with a male and radiographed weekly for two and a half years to track the growth of the lumbar vertebrae as the mole-rats became sexually mature and experienced pregnancies. The lumbar vertebrae of breeding females grew at an increased rate during each pregnancy but growth rates returned to normal between pregnancies and during extended periods without reproduction. The rate of lumbar lengthening was reduced to normal rates in older, established queens experiencing pregnancies. Our results imply that the length of a new queen mole-rat is proportional to the number of pregnancies experienced and suggest that hormones related to pregnancy may play the critical role in bone growth associated with caste transformation.

Cessation of Reproduction‐Related Spine Elongation After Multiple Breeding Cycles in Female Naked Mole‐Rats

The breeding female or “queen” naked mole‐rat has a uniquely elongated body morphology attributed to the lengthening of the lumbar vertebral column that occurs during pregnancy. It is unknown whether this vertebral growth is a continuous process, or associated only with early reproductive experience. We compared pregnancy‐related bone elongation in nascent primiparous queens and established queens to determine if this vertebral expansion was a lifelong process in these females. We also investigated the impact of lactation on vertebral elongation in these mole‐rats because it is known to be a time of significant bone loss in other mammals. Our data show that after eight or more pregnancies, established queens no longer experienced a net gain in lumbar spine length over the reproductive cycle, whereas the nascent breeders demonstrated significant spine lengthening over this time. Despite the lack of net spine lengthening in established breeders, our results indicated that these queens still experienced some pregnancy‐specific vertebral elongation. In naked mole‐rats, pregnancy‐induced bone elongation may serve the dual purposes of first lengthening the spine, and then once optimal spine size is achieved, serving as a homeostatic mechanism that prepares the spine for the mineral demands of lactation. Anat Rec, 2009.

Early Evidence of Low Bone Density and Decreased Serotonergic Synthesis in the Dorsal Raphe of a Tauopathy Model of Alzheimer’s Disease

Reduced bone mineral density (BMD) and its clinical sequelae, osteoporosis, occur at a much greater rate in patients with Alzheimer’s disease (AD), often emerging early in the disease before significant cognitive decline is seen. Reduced BMD translates to increased bone fracture risk, decreased quality of life, and increased mortality for AD patients. However, the mechanism responsible for this observation is unclear. We hypothesize that bone loss is an additional component of an AD prodrome-changes that emerge prior to dementia and are mediated by dysfunction of the central serotonergic pathways. We characterized the skeletal phenotype of htau mice that express human forms of the microtubule-associated protein tau that become pathologically hyperphosphorylated in AD. Using radiographic densitometry, we measured BMD in female and male htau mice from 2–6 months of age–time-points prior to the presence of significant tauopathy in the hippocampal/entorhinal regions characteristic of this model. We found a significantly reduced BMD phenotype in htau mice that was most pronounced in males. Using western blotting and immunofluorescence, we showed overall reduced tryptophan hydroxylase (TPH) protein in htau brainstem and a 70% reduction in TPH-positive cells in the dorsal raphe nucleus (DRN)–a pivotal structure in the regulation of the adult skeleton. Elevations of hyperphosphorylated tau (ptau) proteins were also measured in brainstem, and co-labeled immunofluorescence studies showed presence of ptau in TPH-positive cells of the DRN as early as 4 months of age in htau mice. Together, these findings demonstrate that reduced BMD occurs earlier than overt degeneration in a tau-based AD model and that pathological changes in tau phosphorylation occur in the serotonin-producing neurons of the brainstem raphe in these mice. This illuminates a need to define a mechanistic relationship between bone loss and serotonergic deficits in early AD.