Pain perception is also known as nociception, which is defined as “the neural process of encoding noxious stimuli” (Merskey & Bogduk, 1994). Nociception serves a protective role, alerting an organism to potentially dangerous or life-threatening conditions and resulting in both reflexive and behavioral responses that minimize further injury (Latremoliere & Woolf, 2009). For example, ankle pain serves as a warning to an adolescent athlete of a potential sprain or strain after a fall or being tripped by an opponent while playing soccer. Nociception involves the peripheral (sensory nerves and receptors) and central (spinal cord, brain) nervous systems. At a basic level, sensory receptors receive input from noxious physical stimuli that causes (or potentially causes) tissue damage. Receptor input is then transmitted to select areas of the spinal cord (spinal dorsal horn) via projecting nerve pathways in the peripheral nervous system. Noxious signals are further processed and modified in the spinal cord, before being relayed to a variety of brain structures that encode characteristics of the stimuli including intensity (how strong pain is), quality (sharp vs. aching pain), and emotional aspects (pain-related anxiety or worry) (Lee & Tracey, 2010; Thomas Cheng, 2010). In the 1960s, Melzack and Wall (1965) provided an initial description of this process via the Gate Control Theory of Pain. Their theory accounted for the role that cognitions (thoughts) and affect (emotions) played on the experience of pain, particularly in a loop pattern whereby descending neural pathways from the brain were identified as amplifying or dampening nociception based on organism-specific characteristics such as past pain history, attention to symptoms, and the emotional state of the individual (Melzack & Wall, 1965). The theory has undergone several transformations over the years, and with the advent of sophisticated research in neuroscience, genetics, and imaging, more elegant and complex models have been described. However, the Gate Control Theory of Pain provided a paradigm shift in the field of pain research with its focus on the multiple dimensions of pain and continues to inform pain conceptualization both in clinical and research settings.

The explosion of genetics research in pain has provided new insights into individual differences in pain perception and pain inhibition. As Mogil et al. (1996) noted, considerable variability has been found among people in overall sensitivity to pain as well as responsiveness to certain pain medications. These differences are in part found to be related to genetic makeup. To clarify these individual differences, researchers have used various methods such as studying people with a congenital insensitivity to pain [summary, Gatchel et al. (2007)] as well as family studies. Since pain problems have a tendency to aggregate in families (e.g., Arnold et al., 2004; Buskila & Neumann, 1997), studies have begun to elaborate on the shared genes that result in high heritability of pain conditions. Studies investigating these genetic factors can be done by looking at multiple generations of family members or twins (e.g., Yunus, 1998; Yunus et al., 1999) or by using animal models (mice and rat studies) in which genetic influences are easier to study in a controlled fashion (Mogil et al., 1996). Findings from genetic studies of pain were well summarized by Gatchel et al. (2007) who concluded that neural transmission of pain requires a variety of intricate processes, based upon the proteins and enzymes that form our genetic makeup. Disruption of any step of these processes in an individual can either amplify or reduce nociception, creating a genetic susceptibility to pain.

Identification of clear biomarkers or genetic vulnerability factors in chronic pain is challenging because of the complex and multifactorial nature of these disorders. For example, functional gastrointestinal disorders such as irritable bowel syndrome (IBS) often have a variety of biological mechanisms that are thought to contribute to the etiology, clinical symptoms can differ from one patient to the next, symptom severity can fluctuate over time, and family histories are positive for multiple pain syndromes, not just IBS (Saito, Mitra, & Mayer, 2010). IBS is therefore not considered to be a monogenic disease (a single gene defect), and dozens of genes have been investigated for their contribution to symptom presentation. Family and twin studies suggest that dual gene–environment influences are probably the best explanation for IBS. Thus, familial clustering of IBS may be related to genetic susceptibility as well as shared environmental factors such as similar eating habits, shared adverse life events, social modeling of adaptive or negative coping, and exposure to toxins or microorganisms (Saito et al., 2010). This type of complex relationship between an individual’s genetic makeup and environmental expression of pain is most likely the reason why one adolescent with chronic pain complains of pain with even the lightest touch, yet another adolescent with the same pain condition may be very athletic and play competitive sports without complaining of much discomfort.

Technological advances in brain imaging have allowed a more in-depth exploration of the underlying brain structures and processes involved in the multidimensional experience of pain. Common imaging techniques used to study pain include functional magnetic resonance imaging (fMRI), positron emission tomography (PET), and scalp electroencephalography (EEG) (Lee & Tracey, 2010). In combination, these imaging techniques provide detailed information about neural activity in the brain, regional blood flow, brain structures and anomalies, and evoked potentials which clarify not only nociception but also the functional changes that happen in the brain during various emotional (anxiety) or coping (distraction) efforts. Several brain structures have been identified as centrally active and involved in pain processing including the somatosensory cortex, anterior insula, and anterior cingulate cortex (ACC) (Gatchel et al., 2007; Lee & Tracey, 2010). Moreover, additional involvement of brain regions including the hypothalamus, periaqueductal gray, prefrontal cortex, and cerebellum has been found. Even psychological processes such as catastrophizing, a negative thought process whereby an individual ruminates about pain, have been related to responses in the prefrontal cortex, insula, anterior cingulate cortex, and medial frontal cortex (Campbell & Edwards, 2009; Gracely et al., 2004; Gracely, McGrath, & Dubner, 1978; Seminowicz & Davis, 2006).

As one can surmise from the research discussed so far, there is not always a direct correlation between nociception and the presence of noxious stimuli. For adolescents with some pain conditions like chronic abdominal pain or fibromyalgia, no clear injury, illness, or other noxious trigger has been linked to their persistent, amplified pain. Pain hypersensitivity in these cases seems to result from a host of changes in neuronal pain pathways in the central nervous system and is known as “central sensitization.” Central sensitization represents “an abnormal state of responsiveness to increased gain of the nociceptive system” (Latremoliere & Woolf, 2009, p. 896). In this state of hyperarousal, pain signals can spontaneously occur (with no clear triggering event), result from increasingly low levels of stimulation (minor events result in major pain), or result from an increasingly larger field of receptors to relay stimuli through pain pathways (the greater the number of receptors, the greater the ability to receive and transfer noxious stimuli). At the patient level, chronic pain stemming from central sensitization causes endless frustration for adolescents, who receive repeated negative results on standard medical tests, and their parents, who see their children continue to suffer from unrelenting symptoms.

In addition to genetic and neurological factors, the role of stress is becoming better understood as being an important factor in the onset and maintenance of persistent pain. Stress comes in many forms for adolescents—getting good grades, planning for college, parent–child conflict, peer relationship difficulties, and simply trying to juggle an increasingly busy schedule of activities. Not only can the psychological aspects of stress (tension, irritability, worry) impact the pain experience, but chronic pain by itself serves as a biological stressor which tends to disturb the body’s natural state of homeostasis. This disturbance in homeostasis can cause a series of internal immune and hormonal reactions that attempt to rectify the disruption and restore balance (Melzack, 2005). These reactions include the release of substances to fight off infection and repair tissue damage, as well as the activation of the hypothalamic–pituitary–adrenal (HPA) system, resulting in a further cascade of chemical reactions that ultimately release cortisol, a stress hormone. In small doses, cortisol is an adaptive substance aimed at coping with a situation that threatens the integrity of the body. Prolonged cortisol exposure resulting from chronic stress becomes problematic as it has been shown to reduce immune system functioning and break down tissue in the body, all of which has implications for the maintenance of chronic pain (Bradley, Haile, & Jaworski, 1992). As Melzack (2005) noted, cortisol in and of itself may not be sufficient to trigger chronic pain but may be necessary to create the internal environment whereby chronic pain problems become possible.

The second aspect of the biopsychosocial model of pain emphasizes the role of psychological factors in the pain experience. How adolescents cope with chronic pain varies greatly based upon their age, gender, psychosocial environment, and learning histories. For example, as they grow older, adolescents may use more positive self-talk (a more sophisticated cognitive technique) than younger children, reflective of their maturing cognitive skills. Also, adolescent males and females may differ in their methods of coping with their symptoms with girls showing a stronger tendency to seek social support (Hodgins & Lander, 1997; Lynch, Kashikar-Zuck, Goldschneider, & Jones, 2007; Spirito, Stark, Gil, & Tyc, 1995) and boys using more activity-oriented distraction (Lynch et al., 2007) and a greater number of techniques than girls (Holden, Gladstein, Trulsen, & Wall, 1994).

Both boys and girls report feeling greater efficacy related to pain coping the more frequently they engaged in adaptive coping such as using positive self-statements, behavioral distraction, and cognitive distraction (Lynch et al., 2007). In addition to positive strategies, adolescents can also engage in negative forms of coping (such as catastrophic thinking) that unintentionally worsen the pain experience. Research has shown a significant relationship between higher levels of pain intensity and catastrophizing about pain (Crombez et al., 2003) and generally using more emotion-focused strategies (Merlijn et al., 2003; Reid, Gilbert, & McGrath, 1998). Emotion-focused coping is described as excessive emotional expression or lack of effort to regulate the emotions that occur with the presence of pain (Reid et al., 1998). With their natural tendency of having more labile emotions, adolescents appear to have higher levels of emotion-focused coping than children, and this may be linked to greater functional disability associated with pain (Reid et al., 1998).

Recent studies of psychological coping have developed coping profiles based on the clinical presentation of youth with chronic pain related to their daily functioning, mood factors, and coping styles. “Avoidant copers” tended to catastrophize about their symptoms, avoided normal activities to prevent flare-ups, and showed significant mood problems (typically depression and anxiety symptoms) and higher disability in response to pain (Claar, Baber, Simons, Logan, & Walker, 2008; Walker, Baber, Garber, & Smith, 2008). These patients may be classified as distressed and low functioning (Scharff et al., 2005). Adolescents characterized as being “dependent copers” also reported higher catastrophizing and disability but sought social support and were less isolated. “Self-reliant and engaged copers” were described as more adaptive because they reported greater use of distraction and self-encouragement, less avoidance, and better problem solving. The more frequent use of these proactive techniques was in turn associated with lower levels of anxiety and depressive symptoms in “adaptive copers” (Claar et al., 2008). In other studies, these copers were also described as “high functioning” given their low levels of psychopathology and functional impairment (Scharff et al., 2005). Thus, coping style (adaptive or maladaptive) is one important factor that affects adolescents’ psychological reactions to persistent pain problems.

For some adolescents, the emotional response to pain can be significant and associated with problematic levels of depressive or anxiety symptoms. Adolescents are at a vulnerable age for the development of mood problems in general, as depression tends to increase during this developmental period. The lifetime prevalence of depression in adolescents is 20 % based on findings from the National Longitudinal Study of Adolescent Health (Rushton, Forcier, & Schectman, 2002). Lifetime prevalence of anxiety disorders in the general population of children and adolescents ranges from 9.9 to 13 % (Costello, Mustillo, Erkanli, Keeler, & Angold, 2003; Shaffer et al., 1996). With the addition of a chronic medical problem, the risk for depression and anxiety may increase. In fact, studies have found increased depressive symptoms (Conte, Walco, & Kimura, 2003; Walker, Garber, & Greene, 1993) and generalized anxiety (Conte et al., 2003; Walker et al., 1993) among youth with chronic pain. In a US study investigating abdominal pain and depression in a representative sample of adolescents aged 13–18 years (Youssef, Atienza, Langseder, & Strauss, 2008), 16 % reported significant depressive symptoms based on a screening tool with clinical cutoffs to define cases of depression. The rate of depressive symptoms was significantly higher for adolescents having daily abdominal pain compared to those who experience it rarely (45 vs. 3.2 %). In a Dutch clinical sample of youth with unexplained chronic pain, the prevalence of comorbid psychiatric disorders was estimated using structured diagnostic interviews with parents and psychiatrists’ clinical interviews with patients (Knook et al., 2011). Combining these two sources and using an impairment criterion, 35 % of the youth with chronic pain suffered from a DSM-IV psychiatric disorder. Anxiety disorders were diagnosed nearly as frequently (17.9 %) as depressive disorders (19.1 %) (Knook et al., 2011). The prevalence of concurrent psychiatric disorders is quite striking for adolescents diagnosed with fibromyalgia. In a clinical sample, 67.1 % of adolescents with fibromyalgia had a current DSM-IV diagnosis based on a semi-structured diagnostic interview, and 71.5 % had a lifetime diagnosis (Kashikar-Zuck, Parkins, et al., 2008). Current anxiety disorders were diagnosed more frequently (57.5 %) compared to mood disorders (22.0 %). Unfortunately, not only can anxiety and depression be a response to pain, but common shared brain structures and neurotransmitters, specifically norepinephrine and serotonin which are implicated in the mood–pain connection (Gatchel, 2004), may result in neurobiological changes that maintain both chronic mood and/or pain problems over time (Maletic & Raison, 2009).

Consideration of emotional factors has been found to be important for predicting the long-term trajectories of pain patients through the adolescent years. In a Canadian national sample of youth followed from ages 10–11 to 18–19 years, internalizing symptoms (anxiety/depression) at age 10–11 years predicted persistent high levels of pain at age 18–19, as well as increasing pain severity for headaches, abdominal pain, and back pain over the adolescent years (Stanford, Chambers, Biesanz, & Chen, 2008). Not all research, however, has found that children and adolescents with chronic pain suffer from significant emotional problems (e.g., Kashikar-Zuck, Goldschneider, Powers, Vaught, & Hershey, 2001; Reid, Lang, & McGrath, 1997). The ability to clarify why some adolescents with chronic pain develop mood problems and others do not is important for appropriate treatment planning. One potentially differentiating factor is the degree to which pain disrupts daily functioning and results in the inability to complete expected adolescent roles. Functional disability is characterized by the interruption in psychosocial functioning and physical activities due to pain symptoms (Walker & Greene, 1991). Impairments can occur in the domains of school attendance, academic performance, social life, athletic participation, and family expectations. Psychological factors may be the best predictors of pain-related functional disability (Kashikar-Zuck et al., 2001; Lynch, Kashikar-Zuck, Goldschneider, & Jones, 2006), more so than actual physical damage or pain intensity. Among children and adolescents with chronic pain, depression has been repeatedly found to be strongly associated with and/or a predictor of functional disability (Balague et al., 1995; Claar & Walker, 2006; Gauntlett-Gilbert & Eccleston, 2007; Kashikar-Zuck et al., 2001; Reid et al., 1997). There is some evidence to suggest that this association may be more salient for girls, but not boys (Kaczynski, Claar, & Logan, 2009). Increased depressive symptoms also have been found to correlate with impaired school functioning (absences, school adjustment, scholastic competence, and grade decline) (Logan, Simons, & Kaczynski, 2009).

Overall, results from these studies strongly implicate the role of coping, psychological adjustment, and mood as being an integral aspect of the pain experience in adolescents. These psychological factors clearly contribute to impairments in functioning and must be properly assessed and treated in a comprehensive manner.

The third aspect of the biopsychosocial model emphasizes the importance of the social environment and its impact on the pain experience. Since pain itself is invisible, adolescents must communicate about their pain in some overt form. Their expressions of pain in turn elicit responses from those in their immediate social environment (e.g., parents, teachers, and friends) which further influences the adolescents’ experience of pain and their response to the pain.

Communication of the pain experience is typically done via pain behaviors, which are observable ways of showing pain (Fordyce, Fowler, & DeLateur, 1968; Tesler, Holzemer, & Savedra, 1998) and may be verbal (e.g., complaining, groaning) and/or nonverbal (e.g., limping, wincing, holding area of pain) (Revicki et al., 2009). Research examining the role of pain behavior in adolescents with chronic pain has shown that increased pain behaviors are related to depressive symptoms, functional disability, pain catastrophizing, and poor quality of life (Lynch-Jordan, Kashikar-Zuck, & Goldschneider, 2010), suggesting that persistent expressions of pain may keep adolescents focused on their symptoms. On the other hand, pain behaviors may also be an instrumental method of obtaining reassurance, intervention, or social support from others such as their caregivers (e.g., Hamers, Abu-Saad, van den Hout, Halfens, & Kester, 1996).

Parents are the primary caretakers of adolescents with chronic pain, and a great deal of research has focused on parental influences. Parents must make a host of decisions about how to respond to their adolescents’ symptoms, such as whether or not to give pain medications, send them to school, or exempt them from chores when they are in pain. Palermo and Chambers (Palermo & Chambers, 2005) provided an excellent review in which they highlighted the complex interactive effects of family level variables on pediatric pain and accompanying functional disability. They noted that parent behaviors may both reward and discourage active coping in youth with pain. Reinforcement of poor functioning has been described as “illness behavior encouragement” or “solicitousness” and may have negative consequences for the adolescents who are recipients of this parenting style. Among children with chronic abdominal pain, mothers who self-described as “highly protective” had children with greater healthcare utilization and higher medical costs for gastrointestinal symptom management compared to mothers described as less protective (Walker, Levy, & Whitehead, 2006). In a study investigating a behavioral treatment intervention for headache, children who experienced more maternal rewarding of pain behaviors showed less improvement in headache reduction after treatment and at 1-year follow-up (Osterhaus, Lange, Linssen, & Passchier, 1997). Thus, some evidence suggests that children experience poorer outcomes with a parenting style that may undermine adaptive coping.

It is unclear, however, if solicitous behavior is uniformly associated with negative outcomes. Wall, Holden, and Gladstein (1996) studied parent responses to pain among children with headaches. Interestingly, higher levels of ­child-perceived parental solicitousness were correlated with fewer behavior problems (Wall et al., 1996). In another study of children with abdominal pain, Walker, Claar, and Garber (2002) hypothesized that parental responses would differentially affect pain symptoms, depending on the child’s perceived self-worth and competence. As expected, children reporting lower global self-worth and academic competence showed more somatic symptoms at follow-up when receiving positive parental attention to symptoms. However, no such differences were noted for children with higher self-worth and academic competence, implying resilience to the sometimes negative influence of this parenting style. Similarly, higher levels of parental negative attention were associated with more symptoms at follow-up but only for children with low self-worth (Walker et al., 2002). In a different study, parent solicitousness was related to increased functional disability only among children with higher depression and anxiety. However, this relationship did not hold true for children with lower psychological distress (anxiety or depression) (Peterson & Palermo, 2004). Results from both of these studies provided evidence that parental responses to child pain may interact with individual personality characteristics to produce differential results and that solicitous behavior does not always produce a negative effect on children and adolescents with pain.

In keeping with findings about chronic pain clustering in families (Arnold et al., 2004; Buskila et al., 1993; Groholt, Stigum, Nordhagen, & Kohler, 2003; Merlijn et al., 2003), parents of adolescents with chronic pain often suffer from chronic pain themselves. When two family members share problems with chronic pain, the parent’s ability to cope with their own health problems can have an impact on adolescent coping via social modeling. A parent who is receiving disability benefits due to pain, uses medication or other passive pain management strategies, and rarely engages in physical activity provides a much different model of coping compared to the parent who maintains but adjusts normal activities for pain, uses a variety of behavioral and lifestyle coping strategies, and rarely complains about health issues. A family pain history has been linked to offspring functional status and disability levels. Parents showing increased pain behaviors, disability, and distress tend to have children with more pain complaints (Jamison & Walker, 1992). Children having a parent with chronic pain report increased pain intensity and frequency (Jamison & Walker, 1992), greater pain-related impairment (Schanberg, Keefe, Lefebvre, Kredich, & Gil, 1998), more medication management of pain (Jamison & Walker, 1992), increased illness behaviors, greater school absences, and more visits to the nurses’ office (Rickard, 1988) compared to offspring of healthy parents or parents with a non-pain chronic illness. Children with medically unexplained chronic pain identified more pain models in their environment and more reinforcing consequences to their pain than children with disease-related pain (Osborne, Hatcher, & Richtsmeier, 1989). These findings collectively reinforce the importance of environmental contributions to the expression of pain, whereby the manner in which parents cope and respond to adolescents’ symptoms is as important as the shared genetic vulnerability for pain in the family.

The area of social adjustment and peer relationships of youth with chronic pain has received less empirical attention. In one Dutch study of children and adolescents with chronic pain, 40 % of youth reported impairment in social relationships (changed or less contact with peers) (Konijnenberg et al., 2005). Similar social problems have been noted in other pediatric studies of chronic pain (Kashikar-Zuck et al., 2007; Merlijn et al., 2003), but not all youth with chronic pain show substantial peer problems (Gauntlett-Gilbert & Eccleston, 2007; Guite, Logan, Sherry, & Rose, 2007). It is possible that for some adolescents, social reputation and adjustment may deteriorate over time secondary to pain-related school absences, mood problems, and fewer interpersonal interactions in class. In one study, poor social functioning was predicted by adolescents’ reported functional disability and depressive symptoms but also by dysfunctional parent–child interactions (Gauntlett-Gilbert & Eccleston, 2007). Thus, pain severe enough to disrupt daily functioning and mood may be more likely to have a broader social impact when accompanied by poor parent–child relationships.