Chronic postsurgical pain in children: Current evidence and clinical perspectives

Table 2 Factors that increase the likelihood of developing chronic postsurgical pain

Risk category	Specific risk factors in children
Premorbid factors
Demographic factors	Age at surgery
	Female sex
	Lower socioeconomic status
Genetic factors	Family history of chronic pain (e.g., recurrent abdominal pain, headaches, musculoskeletal pain)
Medical factors	Pre-existing chronic or recurrent pain conditions (e.g., recurrent abdominal pain, headaches, musculoskeletal pain)
	History of prior surgery with persistent pain
	Chronic medical conditions (e.g., sickle cell disease, inflammatory bowel disease, cerebral palsy, obesity)
Injury and recovery factors	Surgery related and early postoperative course
Type, extent, and duration of surgery	High-risk surgeries
	Nerve injury, or re-operation
Acute postsurgical pain	High pain scores in the first 3-7 days postoperatively (e.g., NRS > 6-7)
	Persistent pain beyond expected recovery period
	Pain-related interference with sleep, eating, mobility, or school attendance
Acute pain	Inadequate or delayed analgesia
	Over-reliance on opioids
	Poorly controlled pain despite treatment
Biological factors	Physiological response to surgery
Inflammatory and endocrine response	Strong local/systemic inflammation (e.g., high CRP, IL-6, or TNF-α levels)
	Prolonged pro-inflammatory state after surgery
	Dysregulation of the hypothalamic-pituitary-adrenal axis
Epigenetic factors	Surgery-induced epigenetic changes in pain-related genes (e.g., opioid receptors, ion channels, inflammatory mediators, catechol-O-methyltransferase/opioid receptor mu 1)
Psychosocial factor	Child’s psychological and behavioral responses
Emotional and cognitive factors	General: High trait anxiety, fear of pain, fear of procedure, low self-efficacy
	Pain specific: Pain-related hypervigilance, fear of re-injury, and negative pain beliefs
Behavioral factors	Avoidance of activity, school, sports, or social interaction
	Poor sleep quality, poor adherence to physiotherapy
	Maladaptive coping strategies
Parental and family factors	Parental chronic pain, anxiety, or depression
	Overprotective parenting, illness reinforcement
	Excessive parental utilization of healthcare services
	Family stress or a history of adverse childhood experiences

CRP: C-reactive protein; IL-6: Interleukin-6; NRS: Numerical Rating Scale; TNF-α: Tumor necrosis factor-alpha.