J Integr Neurosci
-
Chronic morphine exposure leads to tolerance, which limits the clinical use of this potent analgesic in the treatment of severe and chronic pain. Compelling evidence suggest that neuro-immune activation (pro-inflammatory cytokines including IL-1β, IL-6 and TNF) as well as neuro-inflammation have been shown to mediate the development of morphine analgesic tolerance. Toll-like receptors (TLRs), especially TLR-4, have also been reported to contribute to the development of morphine analgesic tolerance. ⋯ Hence, we hypothesis the possible involvement of myeloid differentiation primary response protein 88 (MyD88), a key adaptor protein for the TLR and IL-1R families, in the development of tolerance to morphine-induced analgesia. Our study demonstrated that chronic intrathecal morphine injection led to a robust increase of MyD88 expression in rat spinal cord. Sustained elevation of MyD88 may play a role in modulating the development of morphine antinociceptive tolerance.
-
The aim was to investigate the effect of mechanical pain stimulation at the lower back on hemodynamic and oxygenation changes in the prefrontal cortex (PFC) assessed by functional near-infrared spectroscopy (fNIRS) and on the partial pressure of end-tidal carbon dioxide ( PetCO 2) measured by capnography. 13 healthy subjects underwent three measurements (M) during pain stimulation using pressure pain threshold (PPT) at three locations, i.e., the processus spinosus at the level of L4 (M1) and the lumbar paravertebral muscles at the level of L1 on the left (M2) and the right (M3) side. Results showed that only in the M2 condition the pain stimulation elicited characteristic patterns consisting of (1) a fNIRS-derived decrease in oxy- and total hemoglobin concentration and tissue oxygen saturation, an increase in deoxy-hemoglobin concentration, (2) a decrease in the PetCO 2 response and (3) a decrease in coherence between fNIRS parameters and PetCO 2 responses in the respiratory frequency band (0.2-0.5 Hz). ⋯ We highlight that PetCO 2 is a crucial parameter for proper interpretation of fNIRS data in experimental protocols involving pain stimulation. Together, our data suggest that the combined fNIRS-capnography approach has potential for further development as pain monitoring method, such as for evaluating clinical pain treatment.
-
In the limbic system, the anterior cingulate cortex (ACCX) is one of the key areas involved in the close association between pain and emotion. However, neuronal changes in ACCX nociceptive responses after stress conditioning have not yet been quantitatively investigated. We investigated the modulation of nociceptive responses in the ACCX neurons following restraint stress in rats. ⋯ Short-term (3 days) and long-term (21 days) of stress conditioning did not affect these responses significantly. Nociceptive responses evoked by other sites of the body (nose, back and four paws) stimulation were not changed by stress-conditioning, indicating that neural information from the tail is important for emotional system modulation. It is suggested that the emotional/affective part of the pain sensation is strongly modified by stress through neuroplasticity in the ACCX.
-
Human behavior emerges from a complex dynamic interaction between graded and context-sensitive neural processes, the biomechanics of our bodies, and the vicissitudes of our environments. These coupled processes bear little resemblance to the iterated application of simple symbolic rules. ⋯ A prototypical case is when succinct verbal instructions are communicated and are promptly followed by another. How does the brain support such rule-guided behavior? How are explicit rules represented in the brain? How are rule representations shaped by experience? What neural processes form the foundation of our ability to systematically represent and apply rules from the vast range of possible rules? This article reviews a line of research that has sought a computational cognitive neuroscience account of rule-guided behavior in terms of the functioning of the prefrontal cortex, the basal ganglia, and related brain systems.
-
This paper summarizes a behavioral paradigm that was developed as a novel method to dissociate the multidimensional pain experience in rodents. The place escape/avoidance paradigm (PEAP) is based on the assumption that if animals escape and/or avoid a noxious stimulus, then the stimulus is aversive to the animal. ⋯ Additional data is presented to demonstrate the validity of the behavioral paradigm and how the paradigm has been used to test the hypothesis that the affective/motivational dimension of pain can be dissociated and studied independent of sensory pain processing. The behavioral paradigm highlights the emerging trend in the area of pain research and management towards developing more realistic behavioral paradigms to assess nociceptive processing in rodent models of chronic pain.