BACKGROUND: Exposure to repetitive pain during the neonatal period has been shown to have important short and long-term effects on the neurodevelopment of the premature neonate and can contribute to experienced prolonged pain. A uniform taxonomy of neonatal prolonged pain is still lacking to this day which contributes to suboptimal prolonged pain management in neonatal intensive care units. Accordingly, a scoping review exploring the state of knowledge about prolonged pain in preterm neonates hospitalised in the neonatal intensive care unit will contribute to the developing field of neonatal prolonged pain and provide recommendations for clinical prolonged pain management.
OBJECTIVE: To determine the scope, extent, and nature of the available literature on prolonged pain in premature neonates hospitalised in neonatal intensive care units.
METHODS: Scoping review.
METHODS: An electronic search was conducted from inception to November 2023 in the databases of CINAHL, PubMed, Medline, Web of Science, GeryLit.org and Grey Source Index. Included studies discussed concepts related to neonatal prolonged pain such as definitions of prolonged pain, indicators of prolonged pain, contexts that result in prolonged pain, prolonged pain evaluation tools, consequences of prolonged pain and interventions for prolonged pain management.
RESULTS: Key concepts of neonatal prolonged pain were identified in the 86 included articles of this scoping review such as definitions (n = 26), indicators (n = 39), contexts (n = 49), scales (n = 56), consequences of prolonged pain (n = 30) and possible interventions for prolonged pain management (n = 22). Whilst a consensus on a definition has yet to be achieved, no proximate event was shown to cause prolonged pain and a time criterion was identified by authors as being relevant in defining prolonged pain. Interestingly, the context of hospitalisation was identified as being the most indicative of prolonged pain in premature neonates and should guide its evaluation and management, whilst only limited pain management interventions and consequences were discussed.
CONCLUSIONS: The findings of this scoping review contribute to the foundation of growing knowledge in neonatal prolonged pain and shed light on the ambiguity that currently exists on this topic in the scientific literature. This review summarises knowledge of key concepts necessary for a better understanding of prolonged pain and stresses the importance of considering contexts of hospitalisation for prolonged pain evaluation and management in neonatal intensive care units, with the objective of improving developmental outcomes of premature neonates.
CONCLUSIONS: A scoping review reveals that the contexts of prolonged pain in premature neonates hospitalised in the neonatal intensive care unit are essential in guiding its evaluation and management.

Prolonged experimental pain models can help assess cortical mechanisms underlying the transition from acute to chronic pain such as resting-state functional connectivity (rsFC), especially in early stages. This crossover study determined the effects of 24-hour-capsaicin-induced pain on the default mode network rsFC, a major network in the dynamic pain connectome. Electroencephalographic rsFC measured by Granger causality was acquired from 24 healthy volunteers (12 women) at baseline, 1hour, and 24hours following the application of a control or capsaicin patch on the right forearm. The control patch was received maximum 1 week before the capsaicin patch. Following 24hours, the patch was cooled and later heated to assess rsFC changes in response to pain relief and facilitation, respectively. Compared to baseline, decreased rsFC at alpha oscillations (8-10Hz) was found following 1hour and 24hours of capsaicin application for connections projecting from medial prefrontal cortex (mPFC) and right angular gyrus (rAG) but not left angular gyrus (lAG) or posterior cingulate cortex (PCC): mPFC-PCC (1hour:P < .001, 24hours:P = .002), mPFC-rAG (1hour:P < .001, 24hours:P = .001), rAG-mPFC (1hour:P < .001, 24hours:P = .001), rAG-PCC (1hour:P < .001, 24hours:P = .004). Comparable decreased rsFC following 1hour and 24hours (P≤0.008) was found at beta oscillations, however, decreased projections from PCC were also found: PCC-rAG (P≤0.005) and PCC-lAG (P≤0.006). Pain NRS scores following 24hours (3.7±0.4) was reduced by cooling (0.3±0.1, P = .004) and increased by heating (4.8±0.6, P = .016). However, neither cooling nor heating altered rsFC. This study shows that 24hours of experimental pain induces a robust decrease in DMN connectivity that persists during pain relief or facilitation suggesting a possible shift to attentional and emotional processing in persistent pain. PERSPECTIVE: This article shows decreased DMN connectivity that might reflect possible attentional and emotional changes during acute and prolonged pain. Understanding these changes could potentially help clinicians in developing therapeutic methods that can better target these attentional and emotional processes before developing into more persistent states.

UNASSIGNED: Postoperative pain and analgesic use after arthroscopic rotator cuff repair remain important issues that affect rehabilitation and overall outcomes.
UNASSIGNED: To evaluate the pre- and intraoperative factors that may cause prolonged duration of postoperative pain and analgesic use.
UNASSIGNED: Case-control study; Level of evidence, 3.
UNASSIGNED: We included 443 patients who underwent arthroscopic rotator cuff repair and subacromial decompression. Visual analog scale (VAS) scores for pain were obtained preoperatively and at 30 and 90 days postoperatively. Patients were divided into a group who had prolonged postoperative pain (duration ≥1 and <3 months; n = 86 patients) and a group with nonprolonged pain (duration <1 month; n = 357 patients). The following factors were compared between groups: age, sex, body mass index, repair technique, tear size, retraction amount, repair tension, tendon degeneration, preoperative pseudoparesis, symptom duration, application of microfracture to the rotator cuff footprint for marrow stimulation, smoking, degree of fatty degeneration, preoperative narcotic analgesic use, diabetes, acromioclavicular joint degeneration, and preoperative Douleur Neuropathique 4 (DN4) and American Shoulder and Elbow Society (ASES) scores.
UNASSIGNED: Significant differences were seen between the prolonged and nonprolonged groups regarding the median duration of pain (54 vs 27 days, respectively; P < .001) and analgesic use (42 vs 28 days, respectively; P < .001). Significant differences were noted between the groups for symptom duration (P = .007), smoking status (P = .001), degree of fatty degeneration (P = .009), preoperative narcotic analgesic use (P < .001), preoperative DN4 and ASES scores, 30-day VAS score (P < .001), duration of opioid and nonopioid analgesic use (P < .001), tear size (P = .026), and retraction stage (P = .032). Tear size (P = .009), retraction amount (P = .005), preoperative narcotic analgesic use (P < .001), degree of fatty degeneration (P < .001), and preoperative DN4 score (P = .024) were factors independently associated with prolonged postoperative pain and analgesic use.
UNASSIGNED: Patients with larger size tears, retracted tendons, preoperative use of narcotic analgesics, higher tensioned tendon after repair, and Goutallier grade 3 or 4 fatty degeneration faced an increased risk of prolonged postoperative pain and analgesic use after arthroscopic rotator cuff repair. These factors might be mitigated by psychosocial support; gentle, controlled, and individualized postoperative rehabilitation approaches; detailed preoperative evaluation; and closer follow-up of patients who are treated operatively.

Previous research has observed that the speed of alpha band oscillations (8-12 Hz range) recorded during resting electroencephalography is slowed in chronic pain patients. While this slowing may reflect pathological changes that occur during the chronification of pain, an alternative explanation is that healthy individuals with slower alpha oscillations are more sensitive to prolonged pain, and by extension, more susceptible to developing chronic pain. To test this hypothesis, we examined the relationship between the pain-free, resting alpha oscillation speed of healthy individuals and their sensitivity to two models of prolonged pain, Phasic Heat Pain and Capsaicin Heat Pain, at two visits separated by 8 weeks on average (n = 61 Visit 1, n = 46 Visit 2). We observed that the speed of an individual\'s pain-free alpha oscillations was negatively correlated with sensitivity to both models and that this relationship was reliable across short (minutes) and long (weeks) timescales. Furthermore, the speed of pain-free alpha oscillations can successfully identify the most pain sensitive individuals, which we validated on data from a separate, independent study. These results suggest that alpha oscillation speed is a reliable biomarker of prolonged pain sensitivity with potential for prospectively identifying pain sensitivity in the clinic.

The infrapatellar fat pad (IFP) contains nerve fiber endings and is considered to play an important role in the perception of knee pain. However, it is unclear whether and to what degree prolonged pain influences the nociceptive role of the IFP. To answer this question, we established a novel rat model of knee pain in which inflammation is restricted to the IFP. Rats received a single intra-IFP injection of monoiodoacetic acid (MIA) (0.2 mg/10 µL or 1.0 mg/10 µL) in the left knee and a phosphate-buffered saline (10 µL) injection in the right knee as a control. Pain-avoidance behavior and histological changes of the knee joint were measured at multiple time points up to 28 days after MIA injection. Histological analysis showed a transient inflammatory response in the IFP body in the 0.2-mg model, whereas prolonged inflammation followed by fibrotic changes was observed in the 1.0-mg model. Subtle histological alterations were observed in the articular cartilage and IFP surface regardless of the dose. The pain-avoidance behavior test indicated the development of prolonged knee pain throughout the experimental period in the 1.0-mg group. Histological assessments showed a significant increase in calcitonin gene-related peptide (CGRP)-positive nerve fiber endings inside IFPs with fibrosis in newly vascularized surrounding regions. These data suggest that irreversible fibrotic changes in the IFP induce the formation of new vessels and CGRP-positive nerve fiber endings that associate prolonged pain in the joint.

OBJECTIVE: Most fragility fractures of the pelvis (FFPs) are conservatively treated in the early phase. However, the definition of conservative treatment failure and the subsequent treatment protocol is controversial. Fracture progression (FP) sometimes occurs during conservative treatment of FFPs. This study aimed to assess the association between FP and prolonged pain in patients with FFPs receiving conservative treatment.
METHODS: Retrospective case series in a single institution in Japan. A total of 192 consecutive FFP patients were identified during study period. Seventy-nine patients met the inclusion and exclusion criteria. FFPs were diagnosed using both CT and MRI and FP was diagnosed with CT. Patients met criteria for prolonged pain if they had persisting pain after 2 weeks of conservative treatment and had lack of improvement in mobility. The relationship between FP and prolonged pain was analyzed using Fisher\'s exact test.
RESULTS: Of the 79 patients, 18 developed FP. Four of the 18 patients with FP met criteria for prolonged pain. Two of 61 patients without FP had prolonged pain (p = 0.022; odds ratio 8.12). In the entire study cohort, six patients (7.6%) met criteria prolonged pain and underwent elective surgery.
CONCLUSIONS: In patients with FFPs, prolonged pain was associated with FP (p = 0.022, OR 8.12). The presence of prolonged pain might help identify FP. If FP is identified, surgical treatment may be required with cautious follow-up particularly in cases, where FFP progresses to type III or IV fracture.

Kinesin superfamily proteins (KIFs) are molecular motors that typically alter the subcellular localization of their cargos. However, the atypical kinesin KIF26A does not serve as a motor but can bind microtubules and affect cellular signaling cascades. Here, we show that KIF26A maintains intracellular calcium homeostasis and negatively regulates nociceptive sensation. Kif26a-/- mice exhibit intense and prolonged nociceptive responses. In their primary sensory neurons, excessive inhibitory phosphorylation of plasma membrane Ca2+ ATPase (PMCA) mediated by focal adhesion kinase (FAK) rendered the Ca transients resistant to termination, and the peripheral axonal outgrowth was significantly enhanced. Upstream, KIF26A is directly associated with a FERM domain of FAK and antagonizes FAK function in integrin-Src family kinase (SFK)-FAK signaling, possibly through steric hindrance and localization to cytoplasmic microtubules.

A framework for defining pain terms such as acute, persistent, prolonged or chronic pain to newborns was derived from the scientific literature on neonatal pain assessments, previous attempts to define chronic pain and the clinical and neurophysiological features of neonatal pain. This novel framework incorporates the temporal features, localising characteristics, and secondary effects of the pain experienced, as well as the behavioural and physiological response patterns of newborns.
CONCLUSIONS: Although not evidence-based, this framework provides an initial starting point for defining commonly used neonatal pain terms. It will require future revision/refinement based on the accumulating evidence for non-acute pain.

Few observational scales are available for assessing chronic or recurrent pain in children with cancer because overt behavioral signs of chronic pain dissipate as time passes, making them difficult to detect reliably. The Douleur Enfant Gustave Roussy (DEGR) scale developed by Gauvain-Piquard to monitor prolonged pain in children with cancer aged 2-6 years is currently the only validated tool available for this purpose, but is time consuming and difficult to use in daily clinical practice. To shorten composite measurement scales, we developed the Hétero Evaluation Douleur Enfant (HEDEN) scale from the DEGR scale. We present here the process and validation of this scale. Expert consensus was used for the elaboration of HEDEN: 5/10 DEGR items were chosen with three rating levels. Concurrent validity was tested in a first cohort with correlation analysis between HEDEN and DEGR. The HEDEN scale was then validated in a second cohort. In the first step, the study (59 children) showed acceptable correlation between DEGR and HEDEN (r = 0.5), with good reliability (α = 0.61), and interrater agreement (r = 0.62). Subsequent validation in 48 children showed a significant correlation between DEGR and HEDEN (r = 0.6). Reliability was good (α = 0.75), with excellent interrater agreement [r = 0.67 (95% CI: 0.48-0.79)]. On average, the evaluation took 23 minutes (SD = 10.4) for DEGR versus 4.42 minutes (SD = 5.9) for HEDEN. This study shows a good correlation between HEDEN and DEGR scales. HEDEN allows accurate assessment of prolonged pain in young children with cancer.