Dualism, Materialism, and the relationship between the brain and the mind in experiencing pain.

Characterizing the relationship between the brain and the mind is essential, both for understanding how we experience sensations and for attempts to create machine-based artificial intelligence. Materialists argue that the brain and the mind are both physical/material in nature whereas Cartesian dualists posit that the brain is material, the mind is non-material, and that they are separate. Recent investigations into the mechanisms responsible for pain can resolve this issue.

Synaptic sensitization in the anterior cingulate cortex sustains the consciousness of pain via synchronized oscillating electromagnetic waves.

A recent report showed that experiencing pain requires not only activities in the brain, but also the generation of electric fields in a defined area of the anterior cingulate cortex (ACC). The present manuscript presents evidence that electromagnetic (EM) waves are also necessary. Action potentials (APs) encoding information about an injury stimulate thousands synapses on pyramidal neurons within the ACC resulting in the generation of synchronized oscillating (EM) waves and the activation of NMDA receptors.

Toward the unknown: consciousness and pain.

Studies of consciousness are hindered by the complexity of the brain, but it is possible to study the consciousness of a sensation, namely pain. Three systems are necessary to experience pain: the somatosensory system conveys information about an injury to the thalamus where an awareness of the injury but not the painfulness emerges. The thalamus distributes the information to the affective system, which modulates the intensity of the pain, and to the cognitive system that imparts attention to the pain.

The α isoform of cGMP-dependent protein kinase 1 (PKG1α) is expressed and functionally important in intrinsic primary afferent neurons of the guinea pig enteric nervous system.

Background: Intrinsic primary afferent neurons (IPANs) enable the gut to manifest reflexes in the absence of CNS input. PKG1α is selectively expressed in a subset of neurons in dorsal root ganglia (DRG) and has been linked to nociception and long-term hyperexcitability.

Methods: We used immunoblotting, immunocytochemistry, and in vitro assays of IPAN-dependent enteric functions to test hypotheses that subsets of primary neurons of the ENS and DRG share a reliance on PKG1α expression.

A novel inhibitor of active protein kinase G attenuates chronic inflammatory and osteoarthritic pain.

Activating PKG-1α induces a long-term hyperexcitability (LTH) in nociceptive neurons. Since the LTH correlates directly with chronic pain in many animal models, we tested the hypothesis that inhibiting PKG-1α would attenuate LTH-mediated pain. We first synthesized and characterized compound N46 (N-((3R,4R)-4-(4-(2-fluoro-3-methoxy-6-propoxybenzoyl)benzamido)pyrrolidin-3-yl)-1H-indazole-5-carboxamide).