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We report the development and characterization of a novel, injury-free rat model in which nociceptive sensitization after red light is observed in multiple body areas reminiscent of widespread pain in functional pain syndromes. Rats were exposed to red light-emitting diodes (RLED) (LEDs, 660 nm) at an intensity of 50 Lux for 8 hours daily for 5 days resulting in time- and dose-dependent thermal hyperalgesia and mechanical allodynia in both male and female rats. Females showed an earlier onset of mechanical allodynia than males. The pronociceptive effects of RLED were mediated through the visual system. RLED-induced thermal hyperalgesia and mechanical allodynia were reversed with medications commonly used for widespread pain, including gabapentin, tricyclic antidepressants, serotonin/norepinephrine reuptake inhibitors, and nonsteroidal anti-inflammatory drugs. Acetaminophen failed to reverse the RLED induced hypersensitivity. The hyperalgesic effects of RLED were blocked when bicuculline, a gamma-aminobutyric acid-A receptor antagonist, was administered into the rostral ventromedial medulla, suggesting a role for increased descending facilitation in the pain pathway. Key experiments were subjected to a replication study with randomization, investigator blinding, inclusion of all data, and high levels of statistical rigor. RLED-induced thermal hyperalgesia and mechanical allodynia without injury offers a novel injury-free rodent model useful for the study of functional pain syndromes with widespread pain. RLED exposure also emphasizes the different biological effects of different colors of light exposure. PERSPECTIVE: This study demonstrates the effect of light exposure on nociceptive thresholds. These biological effects of red LED add evidence to the emerging understanding of the biological effects of light of different colors in animals and humans. Understanding the underlying biology of red light-induced widespread pain may offer insights into functional pain states. [ABSTRACT FROM AUTHOR]

Context: Ovarian hormone deficiency observed in menopausal women increases the production of reactive oxygen species, which could be implicated in central sensitization subjacent in chronic functional pain syndromes. Aims: To examine the hyperalgesic state induced by ovariectomy in adult rats and its relation to some oxidative stress outcomes. Methods: The female Wistar rats were divided into normal, sham ovariectomized (OVX) and OVX groups, which were tested for mechanical and thermal hypernociception during 6 weeks and a single acetic acid-induced test 6 weeks after surgery. Redox biomarkers determinations of superoxide dismutase (SOD) enzyme activity, glutathione (GSH) and nitrates/nitrites as an indicator of nitric oxide (NO) concentrations were determined in the brain and cerebellum of 6 animals of each group. Results: Exclusivity OVX rats developed a robust state of mechanical hypernociception and allodynia in the abdomen, hindlimbs and proximal tail. Besides, thermal pain thresholds (hot plate) decreased. That was established 3-4 weeks after OVX and lasted for the 6 weeks of the experiment. Increases in visceral sensitivity were also observed in OVX rats. SOD enzyme activity decreased in OVX rats, which showed major deficit for this enzymatic defense under visceral inflammatory injury. However GSH concentrations were increased in brain of OVX animals that allow the balance during acute inflammation. NO concentrations were raised only in OVX rats exposure to chemical inflammatory injury. Conclusions: OVX in rats provide a useful model, which mimics the functional pain in females that could be related with brain oxidative stress.

The response of diffuse noxious inhibitory controls (DNIC) is often decreased, or lost, in stress-related functional pain syndromes. Because the dynorphin/kappa opioid receptor (KOR) pathway is activated by stress, we determined its role in DNIC using a model of stress-induced functional pain. Male, Sprague-Dawley rats were primed for 7 days with systemic morphine resulting in opioid-induced hyperalgesia. Fourteen days after priming, when hyperalgesia was resolved, rats were exposed to environmental stress and DNIC was evaluated by measuring hind paw response threshold to noxious pressure (test stimulus) after capsaicin injection in the forepaw (conditioning stimulus). Morphine priming without stress did not alter DNIC. However, stress produced a loss of DNIC in morphine-primed rats in both hind paws that was abolished by systemic administration of the KOR antagonist, nor-binaltorphimine (nor-BNI). Microinjection of nor-BNI into the right, but not left, central nucleus of the amygdala (CeA) prevented the loss of DNIC in morphine-primed rats. Diffuse noxious inhibitory controls were not modulated by bilateral nor-BNI in the rostral ventromedial medulla. Stress increased dynorphin content in both the left and right CeA of primed rats, reaching significance only in the right CeA; no change was observed in the rostral ventromedial medulla or hypothalamus. Although morphine priming alone is not sufficient to influence DNIC, it establishes a state of latent sensitization that amplifies the consequences of stress. After priming, stress-induced dynorphin/KOR signaling from the right CeA inhibits DNIC in both hind paws, likely reflecting enhanced descending facilitation that masks descending inhibition. Kappa opioid receptor antagonists may provide a new therapeutic strategy for stress-related functional pain disorders. [ABSTRACT FROM AUTHOR]

Abstract: Objective: In psychiatry, pain disorders not explained by structural lesions have been classified for decades as somatoform pain disorders, the underlying concept being somatization. In a parallel move, somatic medicine has defined an expanding group of similar pain disorders, known as functional pain syndromes. Functional pain syndromes are characterized by enhanced pain sensitivity. The aim of our study was to investigate the proportion of patients with somatoform pain disorders who also meet the criteria of functional pain syndromes and the extent to which patients with somatoform pain disorders also show enhanced pain sensitivity. Methods: Data on pain sensitivity in 120 hospitalized patients were obtained by means of two algometric methods. The group of patients with somatoform pain disorders was further divided into two subsets: patients with and those without a co-diagnosis of a functional pain syndrome. Patients with nociceptive pain served as control group. Results: Of the 120 in-patients selected, 67 fulfilled the criteria of a somatoform pain disorder of which 41 (61%) also met the co-diagnosis of a functional pain syndrome. Patients with somatoform pain disorder differed from controls in that they showed enhanced pain sensitivity, irrespective of whether a functional pain syndrome was concomitantly present (P<.001). Conclusions: Somatoform pain disorders show considerable overlap with functional pain syndromes, including enhanced pain sensitivity. This suggests the relevance of integrating somatosensory aspects of pain into a modified understanding of somatoform pain disorders. [Copyright &y& Elsevier]

Objectives: This study was designed to investigate whether an individual and parental history of functional pain syndromes (FPS) is found more often in adolescents suffering from chronic pain than in their pain-free peers. Methods: Our case-control study involved 101 adolescents aged 10-18 years. Cases were 45 patients of the Chronic Pain Clinic at Sydney Children's Hospital with diverse chronic pain disorders. Controls consisted of 56 adolescent volunteers who did not have chronic pain. Adolescents and their parents filled out questionnaires assessing demographic data as well as known and potential risk factors for chronic pain. A history of FPS was assessed by questionnaire, including restless legs syndrome (RLS). Chi-squared tests and t-tests were used to investigate univariate associations between chronic pain in adolescents and lifetime prevalence of FPS. Logistic regression was used to test multivariate associations, while controlling for possible confounders. Results: Migraine, non-migraine headaches, recurrent abdominal pain (RAP), and RLS were reported significantly more frequently in cases than controls (P-values of 0.01, ,0.001, 0.01, and 0.03, respectively). Parental migraine, RAP, and RLS were also significantly associated with adolescent chronic pain in the multivariate analyses. Individual history of migraine, non-migraine headaches, and RAP, along with parental history of RAP and depression significantly accounted for 36%-49% of variance in chronic pain. Other associations with chronic pain were generally in accordance with previous reports. Discussion: It may be helpful when assessing a child who has chronic pain or is at risk of chronic pain, to enquire about these associations. Based on the current findings, an individual history of migraine, non-migraine headaches, and RAP, as well as parental migraine, RAP, and RLS are symptoms that are of particular relevance to assess. [ABSTRACT FROM AUTHOR]

Background: Pain drawings are a diagnostic adjunct to history taking, clinical examinations, and biomedical tests in evaluating pain. We hypothesized that somatoform-functional pain, is mirrored in distinctive graphic patterns of pain drawings. Our aim was to identify the most sensitive and specific graphic criteria as a tool to help identifying somatoform-functional pain. Methods: We compared 62 patients with somatoform-functional pain with a control group of 49 patients with somatic-nociceptive pain type. All patients were asked to mark their pain on a pre-printed body diagram. An investigator, blinded with regard to the patients' diagnoses, analyzed the drawings according to a set of numeric or binary criteria. Results: We identified 13 drawing criteria pointing with significance to a somatoform-functional pain disorder (all p-values ⩽ 0.001). The most specific and most sensitive criteria combination for detecting somatoform-functional pain included the total number of marks, the length of the longest mark, and the presence of symmetric patterns. The area under the ROC-curve was 96.3% for this criteria combination. Conclusion: Pain drawings are an easy-to-administer supplementary technique which helps to identify somatoform-functional pain in comparison to somatic-nociceptive pain. [ABSTRACT FROM AUTHOR]