Reverse-engineering Analysis of Cervical Traction Therapy’s Ability to treat Gastroparesis

Abstract -- Delayed gastric emptying (GE) is called gastroparesis (associated with Irritable Bowel Syndrome -constipation). The following procedure was developed to produce gastric emptying. Drinking coffee is a pre-requisite for the anti-gastro paretic effects of the procedure. The procedure, in a nutshell, is this: for one hour after taking coffee and rocking on one’s side, gastric emptying of coffee is induced (and palpable). The above steps are necessary for the cervical traction device (TD) to function after the application of TD, in which one lies on one’s side while performing neck pulls. The following analysis of the inputs of the procedure uses known research about how the steps of the procedure work
Background:  A study found that the long-term consumption of caffeine can induce ventriculomegaly.  In the caffeine-treated rats with ventriculomegaly, there was increased production of CSF , associated with the increased expression of Na(+), K(+)ATPase  and increased cerebral blood flow (CBF).  In contrast, acute treatment with caffeine decreased the production of CSF, suggesting ‘effect inversion’ associated with caffeine, which was mediated by increased expression of the A1 adenosine receptor, in the chroid plexus (CP) of rats chronically treated with caffeine.  Adenonosine receptor signaling can regulate the production of CSF by controlling the expression of Na(+), K(+) ATPase and CBF, decreased by caffeine, causing decreased CSF production into ventricles.   ANP titers in human CSF have previously been shown to increase proportionally to increments in ICP (intra-cranial pressure).   Therefore, caffeine decreases CSF production via decreased ICP at the CPs.  The above system is directly proportional to AQP1 (aquaporin 1) system expressed at the CP.  AQP is activated by an endogenous receptor guanylate cyclase for atrial natriuretic  peptide (ANP).  AQP1 Current activation decreases the normal basal-to-apical fluid transport equivalent to decreased CSF-pressure.  The cGMP (cyclic Guanosine monophosphate)-gated conductance has properties of permeability to Na+, K+ , and dependence on cGMP.  Thus , AQP1 can function as both a water channel and a gated ion channel.   To maintain CSF-pressure equilibrium, when the Na+, K+ ATPase system increased, (to decrease CSF-pressure), the ANP system must be decreased by receptor internalization, but is at an excess before its elimination.  The excess ANP is a ligand for NPR-A (ANP receptors) receptors via ICP through the central canal to the Fourth ventricle, causing cGMP increasing fluid out.
Stimulation of aquaporin-mediated fluid transport by cyclic GMP with ANP (stimulating the natriuretic signaling pathway , would induce a net apical-to-basal transport of fluid.  NPR-C neutralizes ANP by receptor internalization at the basal lamina of the CP, thus slowing down CSF production.  The distribution of NPR-A in eel was examined .  The immunoreactive neurons in the glossopharyngeal-vagal motor complex were observed via auto-radiography.  
Vagal motor complex activation causes diaphragm contractions.  The crural diaphragm (CD) is the muscular point of attachment of the diaphragm to the thoracic (and lumbar—on the right) spine.  Retrograde tracing revealed a unique population of CD motor neurons in brainstem vagal nuclei.   Electromyography responses of the CD were recorded in vivo.  Electromyography responses in the CD were evoked by vagus nerve stimulation.  Single afferent fibers with receptive fields in the diaphragm dissected from the right phrenic nerve were classified according to reaction to contraction of the diaphragm.  32% of fibers were slightly affected or not affected by diaphragmatic contraction.  They had low- and high-threshold receptive fields located mostly in the muscular part of the diaphragm, and were activated when bradykinin and lactic acid were applied to their receptive fields.  Most of them were group IV afferent fibers.  The discharge of single unit group IV phrenic afferent fibers was recorded during rhythmic diaphragmatic contractions before and after the onset of fatigue.  Compared to pre-fatigue impulse activity, group IV phrenic afferent fibers discharged more during rhythmic diaphragmatic contractions when the diaphragm was fatigued.  I believe that rocking from side to side with the vagal motor complex causing CD contraction causes diaphragmatic fatigue by isometric exercise of the CD.  Phrenic nerve afferents activate neurons in the SI (somatosensory  cerebral cortex), which can be used for diaphragmatic proprioception and somatosensation.  With regard for the specific role SI may play in pain processing, electrphysiological studies in animals and human functional neuroimaging studies have found that SI encodes stimulus intensity, such that phrenic afferents cause normal neck afferents to become noxious pain afferents.  In general, in central nervous system adrenal sympathetic efferent nerve activity and catecholamine secretion increase in response to noxious somatic stimulation. To determine whether noxious movements of the mechanoreceptor-rich deep tissues of the neck modulate the sympathetic outflow to the adrenal glands, a computer driven small animal manipulator was used to impose ramp and hold rotational displacements of the 2nd vertebra while recording multi-unit activity from sympathetic nerves innervations the adrenal gland. The data suggest that noxious stimuli may modulate sympathetic outflow.  
Mesenteric veins are more sensitive than arteries to the constrictor effects of sympathetic nerve stimulation.  Norepinephrine induced constriction from concentration-response curves were left-shifted in veins compared to arteries.   Large amplitude stretch activated sensory endings within the gut wall as extrinsic mechanosensitive afferent nerves on mesenteric blood vessels.  Similar intramural mechanosensitive afferent endings on blood vessels also exist in the colon.  Colonic afferent central terminals in the dorsal horn neurons were activated by colonic stimuli, and were primarily located in doral horn lamina I and V.
The projections of primary afferents from rostral cervical segments to the brainstem and the spinal cord of the rat were investigated by using anterograde transport techniques.  Lateral collaterals projected mainly to the lateral spinal lamina V.  Results from transganglionic staining indicated the lateral collaterals were contributed to by suboccipital proprioceptive fibers.   The spinothalamic tract (STT) arises primarily from cells in lamina I of the dorsal horn, from lamina V cells and respond only to noxious mechanical stimuli.  STT cells of lamina V tend to respond to both innocuous and noxious stimuli.  Using anterograde transport , it was found that there is a substantial projection of the dorsal STT to the posterior nuclei (Po).     There is increased activity in the primary somatosensory cortex (SI) a major projection target of Po that plays an important role in processing sensory-discriminative aspects of pain.   STT axons passed through Po thalamus en route to VP, (I.E. the Po is caudal to the primary somatosensory nuclei,--in  the ventral posterior thalamus).   The Po thalamus palys a qualitiatvely different role in pain sensation from the VP).  Although the role of SI in nociceptive processing is controversial, several lines of evidence support the notion the SI is a key component of the cortical network that is responsible for pain perception.  
Epinephrine increased the contribution of the splanchnic venous blood flow.  These results indicate that venous blood flow increase in the splanchnic vessels largely determined the formation of changes in the IVC blood flow in response the catecholamines.   This causes decreased mesenteric arterial blood flow from the superior and inferior mesenteric arteries, equivalent to decreased extrinsic mechanosensitive afferent nerve discharge projecting to SI causing decreased pain perception.  Therefore, the function of the cervical traction is to secrete adrenaline causing decreased stretch of mesenteric  arteries.  The decreased pain perception of the SI also decreases pain perception of the colon where decreased stretch causes an increase in ileal bile acid transport.  Increased bile acid in the liver decreases systemic triglycerides, making apolipoprotein E (Apo E) unnecessary to deposit triglycerides into the fat cells. (Apo E is important in modulating triglyceride metabolism in adipocytes).  In Apo E-KO (Knock-out) mice, the superoxide derived from NADPH oxidase reacts with NO to form peroxynitrite which induces oxidative degradation of BH4.   Tetrahydrobioperin (BH 4), an essential co-factor for NOS is intracellularly produced from GTP via GTP-cyclohydrolase I and acts as a redox switch in the oxygenase domain of NOS.  Reduced levels of BH4 impair the production of NO and lead to increased superoxide radical production.  BH4 deficiency has been associated with diabetic complications including gastroparesis.  Decreased availability of BH4 and nNOS (neuronal nitric oxide synthase) uncoupling which results in impaired nitrergic relaxation of the pyloric sphincter and thus caused gastroparesis.   Therefore increased levels of APO E should decrease gastroparesis.  Increased gastric emptying should cause a gastro/ colonic reflex producing flatus and bowel movements.  This would decrease colonic stretch further, causing ileal bile acid transport, and eventually causing gastric emptying.
Somatosensory lesions to the hindlimb region altered responses to mec hanical stimulation in the presence of experimentally-induced inflammation, but did not attenuate the inflammation-induced paw volume changes or the level of pain affect.  This demonstrates the presence of pain affect in the absence of somatosensory processing, by inflammatory pain.  In the case of gastroparesis from projecting colon pain, the above may mean that when the colon pain is decreased, the affect of the somatosensory cortex on the adrenals (epinephrine secretion), is still present.