Pain In Early Life Research Articles

Early-life programming of pain sensation? Spinal pain in pre-adolescents with pain experience in early life.

Neurobiological mechanisms can be involved in early programming of pain sensitization. We aimed to investigate the association between early-life pain experience and pre-adolescence spinal pain. We conducted a study of 29,861 pre-adolescents (age 11-14) from the Danish National Birth Cohort. As indicators of early-life pain, we used infantile colic and recurrent otitis media, reported by mothers when their children were 6 and 18 months. Self-reported spinal pain (neck, middle back, and/or low back pain) was obtained in the 11-year follow-up, classified according to severity. Associations between early-life pain and spinal pain in pre-adolescents were estimated using multinomial logistic regression models. To account for sample selection, inverse probability weighting was applied. Children experiencing pain in early life were more likely to report severe spinal pain in pre-adolescence. The association appeared stronger with exposure to two pain exposures (relative risk ratio, 1.31; 95% CI, 1.02-1.68) rather than one (relative risk ratio, 1.14; 95% CI, 1.05-1.24). We observed similar results when using headache and abdominal pain as outcome measures, underpinning a potential neurobiological or psychosocial link in programming of pain sensitization.Conclusion: Experience of early-life pain is seemingly associated with spinal pain in pre-adolescence. The study highlights that early-life painful experiences can influence programming of future pain responses.What is Known:• Spinal pain in pre-adolescents is common, causes marked discomfort and impairment in everyday life, and may be an important predictor of spinal pain later in life.• Neurobiological mechanisms have been suggested as involved in early programming of pain sensitization.What is New:• Pain exposure in early postnatal life in terms of infantile colic and recurrent otitis media is associated with spinal pain in pre-adolescence; thus, experience of such painful conditions in the early postnatal period may seemingly influence programming of future pain sensation.

Recalled early life adversity and pain: the role of mood, sleep, optimism, and control.

Early life adversity (ELA) has been associated with pain symptomatology in adulthood, but mechanisms and moderators of these associations are unclear. Using recall based and concurrently assessed self-report data, we examined associations between ELA, mood, sleep, and recent pain intensity and interference, and whether optimism and perceived control weakened these associations in a midlife community sample of diverse adults reporting some ELA. Controlling for demographic variables and BMI, higher levels of ELA were associated with more pain intensity and interference; greater sleep disturbance and negative mood accounted for these associations. When moderation was examined, only the path from sleep disturbance to pain interference was significantly attenuated for those with higher optimism and higher perceived control. These findings suggest that higher levels of ELA may link with pain in adulthood through poorer mood and sleep, and that resilience resources such as optimism and control may buffer some of these pathways.

Changes in Sleep Architecture under Sustained Pain in Adult Male Rats Subjected to Neonatal Short-Lasting Local Inflammatory Insult

Neonatal, short-lasting, local, nociceptive insult by carrageenan can cause long-term alterations in somatosensory and neurohumoral systems. We previously revealed hyporesponsiveness of the autonomic nervous system (ANS) after painful stimulation of adult rats in a neonatal carrageenan-induced pain model. Sleep disturbance has been highly correlated with pain and ANS activity. In the present study, adult rats that had received an intraplantar injection of carrageenan on postnatal day 1 were investigated to determine if there were alterations in their sleep architecture upon the stimulation of pain. Polysomnographic and heart rate variability recordings were carried out, with a wireless transmission of data, for 24 h under baseline conditions and after an intraplantar injection of complete Freund's adjuvant to induce sustained nociception. Increased active awake (AW) and decreased quiet sleep (QS) and paradoxical sleep (PS) times were noted in the control animals. In the carrageenan-treated rats, the AW time increased but with decreased alertness, as revealed by decreases in beta and increases in theta power. The QS time did not decrease. The PS time decreased during the first 12 h, then increased during the following 12 h, suggesting an early rebound of formerly deprived PS time. Sympathetic activation under sustained pain was not apparent in any stage of sleep in carrageenan-treated rats and was even suppressed in AW time. An impaired sympathetic reaction to pain may have contributed to the atypical changes in sleep architecture in these rats. In conclusion, pain in early life has a long-term effect on the cardiovascular-autonomic-electroencephalographic responses to pain later in life. The physiological relevance of these results remains undetermined.

PEARL-Pain in Early Life: A New Network for Research and Education.

Andersen, Randi Dovland MSc, RN; Axelin, Anna PhD, RN; Kristjánsdóttir, Guðrún PhD, RN; Eriksson, Mats PhD, RN Author Information

Evaluate the Efficacy of Topical Anesthetic on Pain during Venipuncture among the Children

INTRODUCTION: Perception of pain in pediatrics is complex, and entails physiological, psychological, behavioural, and developmental factors. However, in spite of its frequency, pain in infants, children and adolescents are often underestimated and under treated. It has also been shown that infants and children, who experience pain in early life, show long-term changes in terms of pain perception and related behaviour. Professionals in health care settings have a responsibility to reduce pain and anxiety as much as possible to increase patient safety. AIM: The aim of the study is to evaluate the effect of topical anaesthetic on venipuncture pain in children who undergo these procedures repeatedly during the course of their treatment. MATERIAL AND METHODS: A quantitative research approach, quasi experimental in which post-test only control group design without randomization was used to conduct this research study. A sample of 80 children as subjects (40- experiment and 40-control) who required venipuncture for any diagnostic and therapeutic purpose in selected hospitals of Punjab was selected using Non probability convenience sampling technique. RESULTS: The study results depicted that mean pain score (1.1±1.19) in experimental group was statistically significantly different then mean pain score (5.25±2.26) in control group. While comparing the level of pain, it was calculated using chi-square test, it was interpreted that there is statistically significant difference in the level of pain in experimental and control group at 0.05 level of significance. CONCLUSION: The study concluded that the topical anaesthetic cream was effective to reducing the pain during venipuncture among the children in experimental group than control group in selected hospitals of Punjab.

Microglia in health and pain: impact of noxious early life events.

What is the topic of this review? This review discusses the origins and development of microglia, and how stress, pain or inflammation in early life disturbs microglial function during critical developmental periods, leading to altered pain sensitivity and/or increased risk of chronic pain in later life. What advances does it highlight? We highlight recent advances in understanding how disrupted microglial function impacts the developing nervous system and the consequences for pain processing and susceptibility for development of chronic pain in later life. The discovery of microglia is accredited to Pío del Río-Hortega, who recognized this 'third element' of CNS cells as being morphologically distinct from neurons and astrocytes. For decades after this finding, microglia were altogether ignored or relegated as simply being support cells. Emerging from virtual obscurity, microglia have now gained notoriety as immune cells that assume a leading role in the development, maintenance and protection of a healthy CNS. Pioneering studies have recently shed light on the origins of microglia, their role in the developing nervous system and the complex roles they play beyond the immune response. These studies reveal that altered microglial function can have a profoundly negative impact on the developing brain and may be a determinant in a range of neurodevelopmental disorders and neurodegenerative diseases. The realization that aberrant microglial function also critically underlies chronic pain, a debilitating disorder that afflicts over 1.5billion people worldwide, was a major conceptual leap forward in the pain field. Adding to this advance is emerging evidence that early life noxious experiences can have a long-lasting impact on central pain processing and adult pain sensitivity. With microglia now coming of age, in this review we examine the association between adverse early life events, such as stress, injury or inflammation, and the influence of sex differences, on the role of microglia in pain physiology in adulthood.

PEARL – Pain in early life. A new network for research and education

Abstract Aims To establish a network for research and education and to provide expert knowledge to parents and health care professionals about pain in early life. Methods In November 2014 a group of Nordic researchers and research students, committed to the field of pain in early life, gathered for an open lecture day and workshop in Örebro, Sweden. Inspired by the work of the Canadian initiative PICH – Pain In Child Health, the network formulated it’s vision: To be a stabile and competent research and training network within the area of pain in early life. A first collaborate project was designed: “Translation, cultural adaptation and validation of the revised version of the Premature Infant Pain Profile (PIPP-R): An effort to improve pain assessment in infants in the Nordic countries”. Results Fourteen months later, in January 2016, the second PEARL-meeting was held, in Oslo, Norway. The lecture day provided clinically active nurses and physicians from several countries with the latest findings on how to best manage pain in neonatal settings. The network which now consist of 18 researchers from different professions and academic levels presents itself on a five-language website: www.pearl.direct. The PIPP-R project has progressed according to the plan. The PIPP-R is translated into Finnish, Icelandic, Norwegian and Swedish. The cultural adaptation and validation should be finished in fall 2016. The members work on and plan for further collaborate projects. The next two steps are to translate and distribute educational material for parents via Internet and social media, and to establish a research and mas-ters course about pain in early life. The work has been secured by funding from Örebro University and Örebro University Hospital Research Foundation. Conclusions PEARL fulfils the need for a collaborative network for pain in early life researchers in the Nordic countries.

How Do Early Life Experiences Modulate Sexual Function, Stress, and Pain? The Role of Serotonin in Sexual Function

Healthy sexual functioning is an important contributor to individual and relational health and well-being. Sexual pain disorders can significantly negatively impact sexual function. Childhood maltreatment, especially sexual abuse, is associated with sexual dysfunctions in adulthood. The serotonin system appears to play a role in this association, as evidenced by both relationships with serotonin transporter gene mutations and sexual side effects of antidepressants which target the serotonin system. Recent research has focused on novel and successful treatments for sexual pain, including hormone treatment, physical therapy, surgical intervention, and transcutaneous electrical nerve stimulation (TENS). Diagnosis of sexual pain disorders, however, has been complicated by the discordant terminology advanced by different medical associations. Much research on sexual dysfunction does not discriminate pain from other dysfunctions, and additional research is needed to examine these relationships specifically with sexual pain.

Caring for Tube-Fed Children: A Review of Management, Tube Weaning, and Emotional Considerations.

Enteral nutrition is the practice of delivering nutrition to the gut either orally or through a tube or other device. Many children are reliant on enteral feedings to either supplement their nutrition or as a complete source of their nutrition. Managing children on tube feedings requires a team of providers to work through such dilemmas as feeding schedules, weaning from tube feeding, sensory implications of tube feeding, treatment of pain or nausea associated with eating, oral-motor issues, and behavioral issues in the child and family. The purpose of the current review is to summarize the multidisciplinary aspects of enteral feeding. The multidisciplinary team consists of a variable combination of an occupational therapist, speech-language pathologist, gastroenterologist, psychologist, nurse, pharmacist, and dietitian. Children who have minimal oral feeding experience and are fed via a nasogastric or gastrostomy tube often develop oral aversions. Limited data support that children with feeding disorders are more likely to have sensory impairment and that early life pain experiences contribute to feeding refusal. There are inpatient and outpatient programs for weaning patients from tube feeding to eating. The parent-child interaction is an important part of the assessment and treatment of the tube-fed child. This review also points out many information gaps, including data on feeding schedules, blenderized tube feedings, the best methods for weaning children off enteral feedings, the efficacy of chronic pain medications with tube-fed children, and, finally, the necessity of the assessment of parental stress among all parents of children who are tube fed.

Multidimensional response to vaccination pain in very preterm, moderate- to-late preterm and full-term infants at age three months

BackgroundVery early life pain exposure and stress induces alterations in the developing brain and leads to altered pain sensitivity. In premature infants with a history of numerous early postnatal adverse events, behavioral responsiveness and hypothalamic–pituitary–adrenal (HPA) axis reactivity may show alterations as well. AimsWe compared a multidimensional response to a painful situation (vaccination) in three month old infants. The study involved very preterm, moderate to late preterm infants and full-term infants with varying exposure to pain and stress within the first weeks of life. Study designAt the age of three months, we evaluated the infants' reactivity to intramuscular injections for immunization. SubjectsThe study included 61 very preterm infants, 30 moderate to late preterm infants and 30 full-term infants. Outcome measuresWe assessed heart rate recovery, Bernese pain Score and increase of salivary cortisol following vaccination. We also evaluated the flexor withdrawal reflex threshold as well as Prechtl's General Movements. Secondly, we assessed factors potentially influencing pain reactivity such as exposure to pain/stress, gender, use of steroids or opioids and mechanical ventilation. ResultsVery preterm, moderate to late preterm and full-term infants showed different reactivity to pain in all analyzed aspects. Very preterm infants showed a lower level of behavioral and physiologic reactivity and exposure to pain/stress predicted lower cortisol increase. ConclusionAt three months of age, very preterm infants show an altered level of HPA axis reactivity. Efforts aiming at minimizing pain and stress in premature infants should be taken.

Analgesia for Early-Life Pain Prevents Deficits in Adult Anxiety and Stress in Rats

Previous studies in rats have established that inflammatory pain experienced on the day of birth (P0) decreases sensitivity to acute noxious, anxiety- and stress-provoking stimuli. However, to date, the impact of early-life pain on adult responses to chronic stress is not known. Further, the ability of morphine, administered at the time of injury, to mitigate changes in adult behavioral and hormonal responses to acute or chronic stressors has not been examined. P0 male and female Sprague-Dawley rat pups were given an intraplantar injection of 1% carrageenan or handled in an identical manner in the presence or absence of morphine. As adults, rats that experienced early-life pain displayed decreased sensitivity to acute stressors, as indicated by increased time in the inner area of the Open Field, and increased latency to immobility and decreased time immobile in the Forced Swim Test (FST). An accelerated return of corticosterone to baseline was also observed. Morphine administration at the time of injury completely reversed this ‘hyporesponsive' phenotype. By contrast, following 7 days of chronic variable stress, injured animals displayed a ‘hyperresponsive' phenotype in that they initiated immobility and spent significantly more time immobile in the FST than controls. Responses to chronic stress were also rescued in animals that received morphine at the time of injury. These data suggest that analgesia for early-life pain prevents adult hyposensitivity to acute anxiety- and stress-provoking stimuli and increased vulnerability to chronic stress, and have important clinical implications for the management of pain in infants.

Endothelin-1-induced priming to capsaicin in young animals

Endothelin-1 (ET-1) is a known algogen that causes acute pain and sensitization in humans and spontaneous nociceptive behaviors when injected into the periphery in rats. This study sought to examine the effect of ET-1 exposure in the neonatal period on subsequent contralateral capsaicin-induced secondary mechanical hyperalgesia. ET-1 or saline was injected into the left plantar hindpaw on postnatal day 7 (P7). On postnatal day 11 (P11), capsaicin cream or control lotion was applied to the right dorsum hind paw and mechanical paw withdrawal thresholds were measured in the plantar hind paw. In saline control males, P11 administration of capsaicin produced a secondary mechanical hyperalgesia that was still present at 2h. Neonatal priming with ET-1 did not alter the magnitude or the duration of secondary mechanical hyperalgesia in males. In contrast, in control females, P11 administration of capsaicin produced less than 40min of mechanical hyperalgesia. Neonatal priming with ET-1 prolonged the duration of secondary mechanical hyperalgesia in females. Priming with ET-1 on P7 led to a significant increase in capsaicin-induced Fos expression in the dorsal horn of the spinal cord in both males and females compared to controls (p<0.001). These findings further suggest that pain in early life may alter future responses to painful stimuli at both the behavioral and neuronal level.

The consequences of pain in early life: injury‐induced plasticity in developing pain pathways

Pain in infancy influences pain reactivity in later life, but how and why this occurs is poorly understood. Here we review the evidence for developmental plasticity of nociceptive pathways in animal models and discuss the peripheral and central mechanisms that underlie this plasticity. Adults who have experienced neonatal injury display increased pain and injury-induced hyperalgesia in the affected region but mild injury can also induce widespread baseline hyposensitivity across the rest of the body surface, suggesting the involvement of several underlying mechanisms, depending upon the type of early life experience. Peripheral nerve sprouting and dorsal horn central sensitization, disinhibition and neuroimmune priming are discussed in relation to the increased pain and hyperalgesia, while altered descending pain control systems driven, in part, by changes in the stress/HPA axis are discussed in relation to the widespread hypoalgesia. Finally, it is proposed that the endocannabinoid system deserves further attention in the search for mechanisms underlying injury-induced changes in pain processing in infants and children.

Acute and chronic pain in children.

Pain in neonates and children differs to that in adults. One of the many challenges associated with the diagnosis and management of pain in early life is that neonates are non-verbal and therefore incapable of communicating their pain effectively to their caregivers. Early life pain is characterised by lowered thermal and mechanical thresholds, and exaggerated and often inappropriate behavioural reactions to pain. These differing behavioural reactions are underpinned by increased excitability/decreased inhibition within the spinal dorsal horn. This itself is the result of immaturity in the anatomical expression of key neurotransmitters and neuromodulators within spinal pain circuits, as well as decreased inhibitory input to these circuits from brainstem centres, and an immature relationship between neuronal and non-neuronal cells which affects pain response. These differences between early and adult pain impact upon not just acute reactions to pain, but also the incidence, severity and duration of chronic pain. In this chapter, chronic pain in childhood is discussed, as are the structural and functional differences that underpin differences in acute pain processing between adults and children. The ability of pain that occurs in early life to alter life-long pain responding is also addressed.

Neonatal injury rapidly alters markers of pain and stress in rat pups

Less than 60% of infants undergoing invasive procedures in the neonatal intensive care unit receive analgesic therapy. These infants show long-term decreases in pain sensitivity and cortisol reactivity. In rats, we have previously shown that inflammatory pain experienced on the day of birth significantly decreases adult somatosensory thresholds and responses to anxiety- and stress-provoking stimuli. These long-term changes in pain and stress responsiveness are accompanied by two-fold increases in central met-enkephalin and β-endorphin expression. However, the time course over which these changes in central opioid peptide expression occur, relative to the time of injury, are not known. The present studies were conducted to determine whether the observed changes in adult opioid peptide expression were present within the first postnatal week following injury. The impact of neonatal inflammation on plasma corticosterone, a marker for stress reactivity, was also determined. Brain, spinal cord, and trunk blood were harvested at 24 h, 48 h, and 7 d following intraplantar administration of the inflammatory agent carrageenan on the day of birth. Radioimmunoassay was used to determine plasma corticosterone and met-enkephalin and β-endorphin levels within the forebrain, cortex, midbrain, and spinal cord. Within 24 h of injury, met-enkephalin levels were significantly increased in the midbrain, but decreased in the spinal cord and cortex; forebrain β-endorphin levels were significantly increased as a result of early life pain. Corticosterone levels were also significantly increased. At 7 d post-injury, opioid peptides remained elevated relative to controls, suggesting a time point by which injury-induced changes become programmed and permanent.

Long-term dysregulation of brain corticotrophin and glucocorticoid receptors and stress reactivity by single early-life pain experience in male and female rats

Inflammatory pain experienced on the day of birth (postnatal day 0: PD0) significantly dampens behavioral responses to stress- and anxiety-provoking stimuli in adult rats. However, to date, the mechanisms by which early life pain permanently alters adult stress responses remain unknown. The present studies examined the impact of inflammatory pain, experienced on the day of birth, on adult expression of receptors or proteins implicated in the activation and termination of the stress response, including corticotrophin releasing factor receptors (CRFR1 and CRFR2) and glucocorticoid receptor (GR). Using competitive receptor autoradiography, we show that Sprague Dawley male and female rat pups administered 1% carrageenan into the intraplantar surface of the hindpaw on the day of birth have significantly decreased CRFR1 binding in the basolateral amygdala and midbrain periaqueductal gray in adulthood. In contrast, CRFR2 binding, which is associated with stress termination, was significantly increased in the lateral septum and cortical amygdala. GR expression, measured with in situ hybridization and immunohistochemistry, was significantly increased in the paraventricular nucleus of the hypothalamus and significantly decreased in the hippocampus of neonatally injured adults. In parallel, acute stress-induced corticosterone release was significantly attenuated and returned to baseline more rapidly in adults injured on PD0 in comparison to controls. Collectively, these data show that early life pain alters neural circuits that regulate responses to and neuroendocrine recovery from stress, and suggest that pain experienced by infants in the Neonatal Intensive Care Unit may permanently alter future responses to anxiety- and stress-provoking stimuli.

A Single Neonatal Injury Induces Life-Long Deficits in Response to Stress

Approximately 500,000 infants are born prematurely each year in the United States. These infants typically require an extensive stay in the neonatal intensive care unit (NICU), where they experience on average 14 painful and invasive procedures each day. These procedures, including repeated heel lance, insertion of intravenous lines, and respiratory and gastric suctioning, typically result in an inflammatory response, inducing pain and stress in the newborn. Remarkably, the majority of these procedures are performed in the complete absence of pre- or post-emptive analgesics. Recent clinical studies report that former NICU patients have increased thresholds for pain and stress later in life as compared with term-born infants. However, to date, the mechanisms whereby early-life inflammation alters later-life response to stress and pain are not known. The present studies were conducted to determine if neonatal injury impairs adult responses to anxiety- and stress-provoking stimuli. As we have previously reported that early-life pain results in a significant increase in opioid peptide expression within the midbrain periaqueductal gray, the role of endogenous opioids in our behavioral studies was also examined. Male and female rats received an intraplantar injection of the inflammatory agent carrageenan (1%) on the day of birth. In adulthood, animals were assessed for changes in response to anxiety- and stress-provoking stimuli using the open field and forced swim tests, respectively. Injury-induced changes in sucrose preference and stress-induced analgesia were also assessed. As adults, neonatally injured animals displayed a blunted response to both anxiety- and stress-provoking stimuli, as indicated by significantly more time spent in the inner area of the open field and a 2-fold increase in latency to immobility in the forced swim test as compared to controls. No change in sucrose preference was observed. Using in situ hybridization and immunohistochemistry, we observed a 2-fold increase in enkephalin mRNA and protein expression, respectively, in stress-related brain regions including the central amygdala and lateral septum. Administration of the opioid receptor antagonist naloxone reversed the attenuated responses to forced swim stress and stress-induced analgesia, suggesting the changes in stress-related behavior were opioid-dependent. Together, these data contribute to mounting evidence that neonatal injury in the absence of analgesics has adverse effects that are both long-term and polysystemic.

Acute Pain and a Motivational Pathway in Adult Rats: Influence of Early Life Pain Experience

BackgroundThe importance of neonatal experience upon behaviour in later life is increasingly recognised. The overlap between pain and reward pathways led us to hypothesise that neonatal pain experience influences reward-related pathways and behaviours in adulthood.Methodology/Principal FindingsRat pups received repeat plantar skin incisions (neonatal IN) or control procedures (neonatal anesthesia only, AN) at postnatal days (P)3, 10 and 17. When adult, rats with neonatal ‘pain history’ showed greater sensory sensitivity than control rats following acute plantar skin incision. Motivational behaviour in the two groups of rats was tested in a novelty-induced hypophagia (NIH) paradigm. The sensitivity of this paradigm to pain-induced changes in motivational behaviour was shown by significant increases in the time spent in the central zone of the arena (43.7±5.9% vs. 22.5±6.7%, p<0.05), close to centrally placed food treats, and decreased number of rears (9.5±1.4 vs. 19.2±2.3, p<0.001) in rats with acute plantar skin incision compared to naive, uninjured animals. Rats with a neonatal ‘pain history’ showed the same pain-induced behaviour in the novelty-induced hypophagia paradigm as controls. However, differences were observed in reward-related neural activity between the two groups. Two hours after behavioural testing, brains were harvested and neuronal activity mapped using c-Fos expression in lateral hypothalamic orexin neurons, part of a specific reward seeking pathway. Pain-induced activity in orexin neurons of control rats (18.4±2.8%) was the same as in uninjured naive animals (15.5±2.6%), but in those rats with a ‘pain history’, orexinergic activity was significantly increased (27.2±4.1%, p<0.01). Furthermore the extent of orexin neuron activation in individual rats with a ‘pain history’ was highly correlated with their motivational behaviour (r = −0.86, p = 0.01).Conclusions/SignificanceThese results show that acute pain alters motivational behaviour and that neonatal pain experience causes long-term changes in brain motivational orexinergic pathways, known to modulate mesolimbic dopaminergic reward circuitry.

Priming of adult pain responses by neonatal pain experience: maintenance by central neuroimmune activity

Adult brain connectivity is shaped by the balance of sensory inputs in early life. In the case of pain pathways, it is less clear whether nociceptive inputs in infancy can have a lasting influence upon central pain processing and adult pain sensitivity. Here, we show that adult pain responses in the rat are 'primed' by tissue injury in the neonatal period. Rats that experience hind-paw incision injury at 3 days of age, display an increased magnitude and duration of hyperalgesia following incision in adulthood when compared with those with no early life pain experience. This priming of spinal reflex sensitivity was measured by both reductions in behavioural withdrawal thresholds and increased flexor muscle electromyographic responses to graded suprathreshold hind-paw stimuli in the 4 weeks following adult incision. Prior neonatal injury also 'primed' the spinal microglial response to adult injury, resulting in an increased intensity, spatial distribution and duration of ionized calcium-binding adaptor molecule-1-positive microglial reactivity in the dorsal horn. Intrathecal minocycline at the time of adult injury selectively prevented both the hyperalgesia and early microglial reactivity associated with prior neonatal injury. The enhanced neuroimmune response seen in neonatally primed animals could also be demonstrated in the absence of peripheral tissue injury by direct electrical stimulation of tibial nerve fibres, confirming that centrally mediated mechanisms contribute to these long-term effects. These data suggest that early life injury may predispose individuals to enhanced sensitivity to painful events.

Age-Related Changes of Pain Experience in Cerebral Palsy and Healthy Individuals

Pain is a serious problem for many individuals with cerebral palsy (CP). Pain and injury in early life may cause long-term changes in somatosensory and pain processing. Nevertheless, no information exists regarding the influence of age on pain reports and touch sensitivity among persons with CP or the influence of age on the quality of life in individuals with CP. The present cross-sectional study investigated pain characteristics, touch sensitivity, and quality of life in 86 individuals with CP and 115 healthy volunteers. Participants were grouped by age in children (6-10 years), adolescents (11-17 years), and young adults (18-30 years). Touch sensitivity at different body locations were tested by using von Frey monofilaments. Data about pain and quality of life were obtained from a semi-structured interview and questionnaires. Participants with CP reported more pain as well as more reduced touch sensitivity and quality of life than healthy controls. Neither pain reports nor touch sensitivity or quality of life were influenced by age in CP, whereas significant age-related changes were observed in healthy participants. Multiple regression analyses also showed that age was the best predictor of current pain intensity in healthy controls but not in individuals with CP. These findings emphasize the importance of considering the presence of pain at very early ages in CP. Furthermore, these results provide clinicians and researchers with a new age-related psychosocial and psychophysiological perspective to investigate the mechanisms that could be involved in the presence and maintenance of pain in this population.