Which age groups are prone to hyperalgesia due to altered nociceptor function?

Age-Related Vulnerability to Hyperalgesia

Neonates and elderly patients represent the two age extremes most prone to hyperalgesia due to altered nociceptor function, with neonates showing heightened sensitization from early-life stress and elderly patients demonstrating enhanced responses to inflammatory mediators.

Neonatal Period: Critical Window for Nociceptor Sensitization

Early-Life Stress Effects

• Neonates exposed to stress between postnatal days 2-9 develop persistent nociceptor sensitization that manifests as chronic hyperalgesia in adulthood 1, 2
• Adult rats previously exposed to neonatal stress show approximately 22% lower mechanical nociceptive thresholds in skeletal muscle compared to controls 1
• This early-life stress produces overexpression of voltage-gated sodium channel NaV1.7 in nociceptors, contributing to chronic muscle pain that persists into adulthood 2

Developmental Limitations in Pain Processing

• Neonates under 3 days postnatal age cannot develop secondary hyperalgesia (the spread of pain sensitivity to surrounding uninjured tissue), though primary hyperalgesia at the injury site occurs at all ages 3
• By 10 days postnatal age, secondary hyperalgesia becomes evident as spinal cord pain processing matures 3
• Preterm neonates experience 10.0-22.9 painful procedures per day, with repeated exposures causing permanent neuroanatomic changes and altered pain sensitivity lasting into adolescence 4

Clinical Implications for Neonates

• Neonates cannot self-report pain and require multidimensional assessment tools combining physiologic and behavioral indicators 4
• The Society for Maternal-Fetal Medicine notes that neonates show fundamentally different pain responses than adults, including altered physiologic patterns during prolonged pain 5

Elderly Patients: Enhanced Nociceptor Sensitivity

Age-Related Nociceptor Changes

• Aged rats (equivalent to elderly humans) demonstrate significantly greater mechanical and thermal allodynia following inflammatory mediator exposure compared to young rats 6
• Intraplantar injection of bradykinin produces greater thermal and mechanical allodynia in aged versus young rats 6
• Prostaglandin E2 injection causes greater mechanical allodynia in aged rats 6
• Capsaicin (TRPV1 activator) produces greater mechanical and heat allodynia in elderly subjects 6

Mechanism of Enhanced Sensitivity

• Unlike other senses that decrease with age, baseline nociceptor sensitivity to thermal and mechanical stimulation remains intact in elderly patients 6
• The critical difference is that elderly nociceptors show exaggerated responses to inflammatory mediators and tissue injury 6
• During tissue injury and inflammation, nociceptor terminals are exposed to prostaglandins, leukotrienes, serotonin, histamine, and cytokines that upregulate sensitivity—a process called peripheral sensitization 5, 7

Clinical Consequences in Elderly

• Pain is often undertreated in elderly patients, with up to 42% of patients over 70 years old not receiving adequate analgesia for fractures despite reporting moderate to high pain levels 5, 8
• Inadequate pain control in elderly patients increases risk for agitation, aggression, delirium, delayed mobilization, and development of chronic pain 5
• Elderly patients with cognitive impairment are particularly vulnerable, receiving less pain medication and experiencing poorer outcomes than cognitively intact patients 5

Common Pitfalls to Avoid

In Neonatal Care

• Never assume absence of pain behavior means absence of pain—neonates may show passivity and decreased responses during prolonged pain as an energy conservation mechanism 4
• Do not extrapolate pain assessment tools from older children to neonates; use age-appropriate validated tools like N-PASS for neonates 0-100 days 4
• Minimize total procedural exposure as the most effective pain reduction strategy rather than relying solely on pharmacologic management 4

In Elderly Care

• Never assume elderly patients experience less pain than younger patients—studies show elderly adults experience the same pain levels from fractures and dislocations as younger counterparts 5
• Do not withhold analgesia based on concerns about adverse effects; instead, use careful dose titration starting at 25% of standard adult doses in patients over 75 years 5, 9
• Recognize that extensive and proactive evaluation may be necessary to overcome communication barriers, especially in cognitively impaired patients 5

Mechanistic Summary

Both age extremes share vulnerability through peripheral sensitization mechanisms 5, 7:

• Neonates: Early-life stress causes permanent upregulation of pain signaling molecules (NaV1.7, protein kinase Cε) in nociceptors 1, 2
• Elderly: Enhanced nociceptor responses to inflammatory mediators (bradykinin, prostaglandins, TRP channel activators) without baseline threshold changes 6

The World Journal of Emergency Surgery emphasizes that inadequate pain control in both populations leads to increased stress response, systemic inflammation, and long-term complications 5, 8.