Increased Nociceptive Sensitivity and Nociceptin/Orphanin FQ Levels in a Rat Model of PTSD

Abstract

BackgroundClinical studies indicate that post-traumatic stress disorder (PTSD) frequently shares co-morbidity with chronic pain. Although in animals acute stress-induced antinociception is well documented, the effect of PTSD-like stress on nociceptive sensitivity is unclear. Though a few studies measured nociceptive responses at a single time point, no studies have examined changes in nociceptive sensitivity over time following exposure to PTSD-like stress. Nociceptin/orphanin FQ (N/OFQ), an endogenous ligand for the N/OFQ peptide (NOP) receptor, modulates various biological functions in the central nervous system that are affected by PTSD, including nociceptive sensitivity, stress and anxiety, learning and memory.ResultsThe present study examined thermal and mechanical nociceptive sensitivity in male Sprague Dawley rats between 7 and 28 days after single-prolonged stress (SPS), an established animal model for PTSD. Rat paw withdrawal thresholds (PWT) to von Frey and paw withdrawal latencies (PWL) to radiant heat stimuli, respectively, dramatically decreased as early as 7 days after initiation of SPS and lasted the length of the study, 28 days. In addition, N/OFQ levels increased in cerebrospinal fluid (CSF; on days 9, 14 and 28) and serum (day 28), while levels of circulating corticosterone (CORT) decreased 28 days after initiation of SPS. SPS exposure induced anxiety-like behavior and enhanced inhibition of the hypothalamo-pituitary-adrenal (HPA) axis, as previously reported for this model.ConclusionsOur results demonstrate that SPS induces the development of persistent mechanical allodynia and thermal hyperalgesia that is accompanied by increased N/OFQ content in the CSF, and eventually, in serum. These findings suggest a link between N/OFQ and the development of hyperalgesia and allodynia in a rat model of PTSD.

Repeated exposure to neurotoxic levels of chlorpyrifos alters hippocampal expression of neurotrophins and neuropeptides

“…They are involved in the regulation of various physiological processes and participate in modulating neurological functions in the brain (Borroni et al, 2009). Expression of these neuropeptides is critical in maintaining normal physiological balance and neurobehavioral functions, such as memory, learning and resilience to stress (Zhang et al, 2012). Conversely, dysregulation of these neuropeptide genes is associated with detrimental consequences, especially in neurobehavioral functions (Table 6).…”

An Overview of Translationally Informed Treatments for Posttraumatic Stress Disorder: Animal Models of Pavlovian Fear Conditioning to Human Clinical Trials

“…Similarly, antagonism of the κ opioid receptor blocks conditioned fear on a fear-potentiated startle paradigm (132, 133). In PTSD-like rodent models, differential levels of CSF nociceptin (NOP)/orphanin FQ and nociceptin (NOP)/orphanin FQ receptor mRNA are observed (134, 135). Furthermore, nociceptin (NOP)/orphanin FQ receptor agonist administration blocks contextual and cued fear consolidation in normal and PTSD-like rodent models (135–137).…”

Predator odor stress alters corticotropin-releasing factor-1 receptor (CRF1R)-dependent behaviors in rats

“…In animals, a single intense stress or chronic stress produces hyperalgesia (Boccalon et al, 2006; da Silva Torres et al, 2003; Geerse et al, 2006; Quintero et al, 2000; Zhang et al, 2012), increases anxiety-like behaviour, and produces hyperarousal in rats (Campos et al, 2013; Kinn Rød et al, 2012; Serova et al, 2013). Alcohol dependence also promotes hyperarousal and hyperalgesia (i.e., increased nociception), each of which may promote compulsive alcohol drinking (Edwards et al, 2012; Egli et al, 2012; Koob, 1999).…”