Frequency Dependent Electrical Stimulation of PFC and ACC for Acute Pain Treatment in Rats

Abstract

As pain consists of both sensory and affective components, its management by pharmaceutical agents remains difficult. Alternative forms of neuromodulation, such as electrical stimulation, have been studied in recent years as potential pain treatment options. Although electrical stimulation of the brain has shown promise, more research into stimulation frequency and targets is required to support its clinical applications. Here, we studied the effect that stimulation frequency has on pain modulation in the prefrontal cortex (PFC) and the anterior cingulate cortex (ACC) in acute pain models in rats. We found that low-frequency stimulation in the prelimbic region of the PFC (PL-PFC) provides reduction of sensory and affective pain components. Meanwhile, high-frequency stimulation of the ACC, a region involved in processing pain affect, reduces pain aversive behaviors. Our results demonstrate that frequency-dependent neuromodulation of the PFC or ACC has the potential for pain modulation.

Combined Transcriptomic and Proteomic Profiling of the Mouse Anterior Cingulate Cortex Identifies Potential Therapeutic Targets for Pulpitis-Induced Pain

“…Currently, the mechanisms underlying pulpitis-induced pain were primarily at the peripheral level, with limited research on central mechanisms. ,− , While it is known that ACC was activated during pain, − ,, its involvement in pulpitis-induced pain remained unclear. To address these gaps, we conducted transcriptomic and proteomic analyses and verified the key DEGs and DEPs by qRT-PCR in the ACC of pulpitis models.…”

“…Among them, ACC plays an important role in pain sensation and pain-related affective emotions. Neurons in ACC were activated in acute and chronic pain. − However, whether ACC is involved in pulpitis-induced pain remains unknown.…”

Translational aspects of deep brain stimulation for chronic pain

“…Similar to other brain structures, the ACC opioid system is critical to selectively modulate the aversive quality of noxious mechanical stimulation in neuropathic pain models ( 97 ). In rodents, ACC high-frequency stimulation reduced aversive pain responses induced by mechanical nociceptive stimuli, while low-frequency stimulation increased pain aversive behaviors ( 98 ). Optogenetic or chemogenetic stimulation of the ACC reduced abdominal hyperalgesia and pain-related anxiety in a rat model of chronic pancreatitis ( 99 ).…”

Synaptic Plasticity in the Pain-Related Cingulate and Insular Cortex

“…Activation of cortical fibers projecting from the somatosensory cortex I (S1) to the ACC enhance hyperalgesia and direct stimulation of the rACC also enhances the nociceptive response to colorectal distension (CRD) [ 9 ]. Further studies have observed that stimulation frequencies between 20 and 100 Hz delivered to the ACC can enhance aversive pain behavior and potentiate spinal excitatory transmission while higher frequency (120 Hz) stimulation was observed to reduce aversive pain in response to mechanical stimuli [ 10 , 11 ]. In addition, high-intensity electrical and chemical stimulation of metabotropic glutamate receptors (mGluRs) within the ACC produces a faciliatory effect on spinal nociception while also contributing to the formation of long-term contextual and auditory fear memory [ 12 , 13 ].…”