Accepted

Functional abdominal pain disorders (FAPD) are common among young individuals. To date, relatively little is known regarding the function of the endogenous analgesic mechanisms in this vulnerable group. Therefore, this case-control study aimed to compare conditioned pain modulation (CPM), pressure algometry and psychosocial variables in 39 young children (aged 6-12 years) with FAPD and 36 age-and sex-matched pain-free controls. Pressure algometry was used to assess pressure pain thresholds at both symptomatic (umbilicus) as remote (trapezius and tibia) test sites. CPM was recorded as an increase in the pressure pain threshold at the trapezius test site in response to experimental conditioning pain imposed by the cold pressure task (12°C ± 1°C). The assessors were blinded to the diagnoses. Parent-proxy and/or self-reported questionnaires were used to assess child's pain intensity, functional disability, pain-related fear and parental pain catastrophizing. Compared with pain-free controls, young children with FAPD showed lower pressure pain thresholds at all test sites (P<0.05), a lower CPM response (P=0.02), more functional disability (P<0.001) and pain-related fear (P<0.001). Parents of children with FAPD catastrophized more about their child's pain than parents of healthy children (P<0.001). No sex differences were found for the experimental pain measurements (P>0.05), nor was there a significant correlation between the child-and parent questionnaires and the CPM-effect (P>0.05). In summary, young children with FAPD demonstrated secondary hyperalgesia and decreased functioning of endogenous analgesia.

Although chronic postsurgical pain (CPSP) is a major health care problem, pain-related functional interference has rarely been investigated. Using the PAIN OUT registry we evaluated patients' pain-related outcomes on the first postoperative day, and their pain-related interference with daily living (Brief Pain Inventory) and neuropathic symptoms (DN4: douleur neuropathique en 4 questions) at six months after surgery. Endpoints were pain interference total scores (PITS) and their association with pain and DN4 scores. Furthermore, possible risk factors associated with impaired function at M6 were analyzed by ordinal regression analysis with PITS groups (no to mild, moderate and severe interference) as a dependent three-stage factor. Odds ratios (OR) with 95% confidence intervals (CI) were calculated. Of 2,322 patients, 15.3% reported CPSP with an average pain score ≥3 (NRS 0-10). Risk for a higher PITS group increased by 190% (OR (95%-CI): 2.9 (2.7-3.2); p<0.001) in patients with, compared to without CPSP. A positive DN4 independently increased risk by 29% (1.3 (1.12-1.45), p<0.001). Pre-existing chronic pain (3.6 (2.6-5.1); p<0.001), time spent in severe acute pain (2.9 (1.3-6.4); p=0.008), neurosurgical back surgery in males (3.6 (1.7-7.6); p<0.001) and orthopedic surgery in females (1.7 (1.0-3.0); p=0.036) were the variables with strongest association with PITS. PITS might provide more precise information about patients' outcomes than pain scores only. As neuropathic symptoms increase PITS, a suitable instrument for their routine assessment should be defined.

The role of sex hormones on postsurgical pain perception is basically unclear. Here we studied the role of endogenous gonadal hormones for pain and hyperalgesia in human volunteers after experimental incision.A 4-mm incision was made in the volar forearm of 15 female volunteers both in the follicular and the luteal phase (random block design). Somatosensory profiles were assessed at baseline and 1-72 h after incision by quantitative sensory testing (QST), compared between both cycle phases and related to individual plasma levels of gonadal hormones.Sensory testing at baseline revealed significantly lower pain thresholds (25 vs. 46 mN, p<0.005) and increased pain ratings to pinprick (0.96 vs. 0.47, p<0.0001) in the luteal phase; similar, one hour after incision, pain intensity to incision (38 vs. 21/100, p<0.005), pinprick hyperalgesia by rating (p<0.05) and area of secondary hyperalgesia (p<0.001) were enhanced in the luteal phase. Multiple regression analysis revealed that pinprick pain sensitivity at baseline was significantly predicted by progesterone (partial r= 0.67, p<0.001), FSH (partial r=0.61, p<0.005) and negatively by testosterone (partial r=-0.44, p<0.05). Likewise, incision-induced pain and pinprick hyperalgesia (rating and area) were significantly predicted by progesterone (partial r=0.70, r=0.46 and r=0.47, respectively; p<0.05-0.0001) and in part by FSH; the contribution of estrogen, however, was fully occluded by progesterone for all measures.In conclusion, pinprick pain as well as incision-induced pain and mechanical hyperalgesia were greater in the luteal phase and predicted by progesterone suggesting a major role for progesterone. Other hormones involved are testosterone (protective) and in part FSH.