Resolving the contributions of anaesthesia, surgery, and nerve injury on brain derived neurotrophic factor expression in the medial prefrontal cortex of male rats in the CCI model of neuropathic pain

Abstract

The medial prefrontal cortex (mPFC) is critical for selecting and shaping complex behavioral responses. In rodent models of neuropathic pain there is evidence for both structural and functional changes in the mPFC. Brain derived neurotrophic factor (BDNF) plays a critical role in the normal functioning of the mPFC. It has been suggested that the disruption of complex behaviors and mood seen in some neuropathic pain patients is mediated in part by alterations of BDNF in this cortical region. In Sprague-Dawley rats, mPFC levels of BDNF and TrkB mRNA and protein, were quantified and compared to controls (n = 24) 6 days after either: (a) halothane (1.5%) anaesthesia (n = 12), (b) sham surgery under halothane (n = 12), (c) sciatic nerve chronic constriction injury under halothane (n = 48). The social behaviors of the rats were quantified daily during the experimental period. Halothane anaesthesia increased BDNF and TrkB mRNA bilaterally. These increases were reversed in rats that underwent sham surgical and nerve injury procedures. Further, halothane anaesthesia, surgical procedures, and nerve injury each decreased BDNF protein levels. These results reveal a marked and distinct BDNF expression profile in the mPFC of rats that have undergone each stage of the procedure to produce neuropathic pain by chronic constriction injury of the sciatic nerve. The highly sensitive nature of neurotrophic signalling to general anaesthesia in the mature neuronal circuit of the adult rat brain highlights the importance of careful evaluation and interpretation of data evaluating the effects of experimental procedures on neural substrates.

Isoflurane but Not Halothane Prevents and Reverses Helpless Behavior: A Role for EEG Burst Suppression?

“…Of particular note, Antila et al (2017) recently attributed the antidepressant-like behavioral effects of ISO in rodents to an increase in TrkB signaling among parvalbumin interneurons. However, these authors and others ( Kang et al, 2017 ) have shown that both HALO and ISO increase TrkB signaling, implying both anesthetics should exhibit similar antidepressant effects in rodents—a prediction that is not supported by our findings.…”

Multidimensional Pain Modulation by Acupuncture Analgesia: The Reward Effect of Acupuncture on Pain Relief

“…The lateral PFC provides direct or indirect glutamatergic neural projections to the VTA, activates VTA DA neurons, releases DA, and produces reward-related behaviors [ 34 ]. Moreover, the PFC, as an essential component of the “pain matrix,” is a critical brain region that regulates pain emotions and participates in pain-related reward and cognition functions [ 35 , 36 ]. Enhancement of neuronal activity in the reward circuit associated with the PFC is a common feature in the formation of chronic pain relief and a core structure of the pain-related brain reward or reinforcement system [ 37 ].…”

Characterization of acute pain‐induced behavioral passivity in mice: Insights from statistical modeling

“…Confusingly, increased open-field thigmotactic behavior can occur in pain models both with and without accompanying amygdala sensitization or neuroplasticity changes (Li et al, 2010;Morland et al, 2015Morland et al, , 2016. Interestingly, the three surgical stages in inducing traumatic neuropathy (anesthesia, deep fascia incision, and nerve damage) induce distinctive patterns of BDNF expression in the medial prefrontal cortex (emotion-processing center) of rats (Kang et al, 2017), hinting that neurochemical alterations contributing to early affective-motivational changes may have occurred during anesthesia and initial tissue inflammation.…”