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Pathophysiology and Cervical Traction Treatment of Gastroparesis associated with constipation-predominant IBS

Posted by screeb , 22 March 2013 · 2,990 views

Pathophysiology and Cervical Traction Treatment of Gastroparesis associated with constipation-predominant IBS Mechanisms Involved in stress-induced modulation of visceral pain.

Pathological pain refers to conditions characterized by hyperalgesia and allodynia, in which maladaptive neuroplastic changes lead to persistent increased perception and responsiveness to noxious stimuli, or response to normally non-noxious stimuli.  Such neuroplastic changes can occur in primary afferent terminals (peripheral sensitization) but also in the spinal cord (central sensitization) and in the brain (supraspinal pain modulation) or in descending pathways that modulate spinal nociceptive transmission.  Such alterations in the processing of sensory information are all considered as possible mechanisms of visceral hypersensitivity in IBS patients.

Animal models showed the modulation of novel non-invasive techniques to assess visceral pain such as intraluminal colonic pressure by allowing for the monitoring of stress-related analgesic pain pathways in the viscera.  Interoceptive stress is defined as a type of stress induced modulation that is limbic in-sensitive, where cognitive processing is bypassed, (i.e. sensory visceral nerves project to brain stem loci such as the locus coeruleus.  Exteroceptive stress is limbic sensitive where manuvers such as water avoidance stress, colorectal distension, and the visceromotor reflex can produce exteroception.

Also, there is mounting evidence that stress can affect the intestinal and fecal microbiota, which display changes in composition, diversity and number of gut microorganisms.  These alterations in the microbiota can in turn have significant impact on the host and affect his behavior, visceral sensitivity, and inflammatory susceptibility.  Stress-induced intestinal epithelial permeability leads to the sensitization of peripheral terminals.  Mechanisms can account for the sensitization of afferent fibers.  In response to inflammation, the intestinal mucosa leads to the release of chemical mediators which can directly stimulate afferent neuron terminals but also promote the release of algogenic substance such as SP or serotonin—leading to the amplification of the afferent stimulus, (see Figure 1—also Reference).

The evidence of mast-cell activation in colonic mucosa is increased colonic mucosal permeability in response to fecal supernatants from patients with IBS, i.e. mucosal mast cell mediators.[1]  Mucosal mediators stimulated longitudinal muscle myenteric plexus (LMMP) preparation, which potentiated cholinergic twitch contractions, an effect directly correlated with mast cell counts.  Therefore, colonic mucosal mediators from patients with IBS excite myenteric cholinergic motor neurons.[2]  Based on the concept that mucosa-nerve signaling is altered in IBS, all IBS supernatants evoked a significant spike discharge in 46% of submucous neurons.  Individual application of the components of the supernatant, revealed that only serotonin evoked a significantly stronger activation of submucous neurons.  The enterochromaffin cell (EC cell), which also senses alterations in luminal or mucosal oxygen levels, is physiologically sensitive to fluctuations in oxygen levels.  Reducing Oelevated 5-HT secretion (2-3.2 fold).  Constipation predominant IBS was associated with decreased plasma 5-HT.  During fasting, the blood flow is low (5% of cardiac output), which then rises significantly to 30% after a meal, increasing PO2.  Alterations in 5-HT release are critically relevant to the regulation of normal function: EEC cells mediate gut secretion, peristalsis, and motility by the secretion of 5-HT.[3] [4] Therefore, when gastric emptying is activated by TD at the colon, increased PO2 levels decrease 5-HT release and decrease distal colon contractions associated with c-IBS.  Inversely, gastroparesis associated with decreased PO2 and increased 5-HT levels, would decrease colon contractions associated with c-IBS.  Any procedure able to increase intra-mural pressure is equivalent to an increase in colonic distension.  This brings us back to the definition of Interoceptive modulation where cognitive processing is bypassed, (i.e. sensory visceral nerves project to brainstem loci such as the locus coruleus or nucleus tractus solitarius). 

Pathophysiology of Gastroparesis

Proximal colon distension causes decreased gastric emptying (increased gastric stasis time in the stomach).[5]  The decreased gastric emptying pathway is blocked by systemic capsaicin.  Capsaicin-sensitive vagal afferent neurons contribute to the detection of pathogenic bacterial colonization in the gut, (which can reduce inflammation and disease activity via the cholinergic anti-inflammatory pathway).[6]  Diminished vagal sensory processing contributes to upper gastrointestinal dysmotility, (see Figure 2).  Therefore, it is possible that proximal colon distension is equivalent to pathogenic bacteria, in that both are capsaicin-sensitive vagal pathways leading to gastroparesis.  This theory is backed-up by the fact that there are no acute pain pathways that are sensed exteroceptively, i.e. in the limbic system directly.  The normal pathway for vagal afferents which project to the NTS, is to project to  the Dorsomotor Nucleus of the Vagus (DMNV), (causing excitiation or inhibition of gastric emptying, [see Figure 2)].[7]

TD use and theory.

The following is a theory to explain the increase in sympathetic vertebral plexus output to the trigeminocervical complex (Vc1-3) to be described below.  Cervical traction causes the sympathetic plexus surrounding the vertebral arteries to be stretched and stimulated.[8]  The deep pathway (vertebral nerve and its branches) with the superficial pathways (the sympathetic trunk and its branches) formed a sympathetic nervous “plexus” in the cervical region.[9]

Cervicogenic  headache is defined as pain perceived in the head, but whose source lies in the convergence between trigeminal afferents and afferents from the upper three cervical spinal nerves (Vc1-3).  The afferents to the spinal nerves C1-C3  must include those originating in the vertebral canal, forming a longitudinal strand of nerve fibers, the sinuvertebral nerve (SVN).  SVNs arose from two roots, a root from the spinal nerve and a sympathetic root from the vertebral artery plexus.  The vertebral canal, (see Figure 4), formed a longitudinal strand of nerve fibers, the SVN which is  a branch of the spinal nerve that reentered the spinal canal and supplied bone and blood vessels.  The nerve originated from the spinal nerve and was joined by a sympathetic  branch, the vertebral nerve plexus around the vertebral artery.  A detailed description of the SVN’s was published, the purpose of which was to demonstrate the origin(s), course, and branches of the SVNs at the C0-C1, C1-C2, C2-C3 intervertebral levels and their distribution to posterior cranial fossa.   The conclusion was that the physiologic basis for pain arising from cervicogenic headaches is convergence between trigeminal afferents and afferents form the upper three cervical spinal nerves.  A source for the origin of cervicogenic headache maybe mediated through the upper cervical SVN nerves, because they supply the dura of the posterior cranial fossa and ligaments of the craniovertebral junction, which convey pain sensation from the dorsal head and neck region.[10]

Migraine pathophysiology involves the trigeminal innervation of the dura mater and intracranial blood vessels.  Electrical stimulation of dural blood vessels is painful and causes activation of neurons in the caudal trigeminal nucleus.  The hypothalamic neuropeptide orexin A synthesized in the lateral and posterior hypothalamus and is involved in nociceptive processing.  The effect of orexin A was examined on responses of neurons in the trigeminal nucleus caudalis.  Orexin-A was able to inhibit dural responses to electrical stimulation via activation of the orexin-A receptor [OX(1)R].[11]

It can be shown that Dopamine, (DA2) family receptors are more often seen in trigeminocervical neurons than Dopamine (DA1) family receptors, and that dopamine locally inhibits trigeminovascular nociceptive transmission.  Orexinergic neurons in the posterior hypothalamus are activated when trigeminovascular nociceptive afferents are stimulated.  Orexin A activation of the OX(1) receptor can modulate dural-vascular responses to trigeminal afferent activation in the trigeminocervical complex.[12]

Orexins are neuropeptides made exclusively in the hypothalamus, and those in the lateral hypothalamus (LH) are involved in reward processing (DA-dopamine).  Related studies showed that LH orexin neurons that project to ventral tegmental area (VTA) had greater Fos induction than non-VTA –projecting orexin neurons, indicating that the VTA is an important site of action for orexin’s role in reward processing.  Antinociceptive effects for two doses of intra-LH carbachol (a cholinergic agonist), was evaluated.  Animals received intra-VTA infusions of SB334867 as a selective orexin A receptor antagonist, just 5 min before microinjection of an effective dose of carbachol into the LH.  Intra-LH administration of carbachol induced antinociception but intra-VTA doses of SB334867, 5min before microinjection of carbachol could prevent the development of antinociception.[13]

Therefore, orexinergic projections from the LH to the VTA are directly involved in the antinociception induced by LH chemical stimulation and orexin-1 receptors in the ventral tegmental area.  Decreased orexin signaling in the brain may play a role in the pathophysiology in patients with functional gastrointestinal disorders accompanied with the inhibition of gut function.  Endogenous orexin-A in the brain mediates 2-deoxy-D –glucose (2-DG) induced stimulation of gastric motility.  2-DG, a central vagal stimulant, significantly increased orexin-A, (and also was suppressed by SB334867 as was carbachol as described above).[14]

Coffee causes decreased blood glucose and when glucose concentrations in the brain fall, orexin A secretion in the lateral hypothalamic are (LHA) increases.   Chlorogenic acids in coffee modulate glucose uptake and 400 mL caffeinated coffee (equivalent to 2.5 nmol chlorogenic acid/L), delayed intestinal glucose absorption.[15] The chlorogenic acids (CGA) work in the stomach at the stomach wall to prevent the sugar emptied into the duodenum from being “sucked up/absorbed.” [16]   The coffee’s prophylactic reduction of glucose absorption at the duodenum would cause glucose to be increased at the portal vein, (as it would be if sugar were present at the duodenum): however, gastric emptying of coffee’s caffeine enhances NHGU (net hepatic glucose uptake) during a glucose load. [17]  More than half of all the body’s glucose is stored as glycogen in muscle and liver, but exercise (rocking) depletes glycogen and a method for the synthesis of sugar from non-carbohydrate precursors is needed.  This is accomplished by a pathway called gluconeogenesis (“new formation of sugar”).   CGA has specifically been shown to inhibit an enzyme, glucose-6-phosphatase, that promotes gluconeogenesis (the formation of glucose in the liver). [18]  This enzyme is found on the endoplasmic reticulum of hepatocytes (mostly), but not in other tissues, which are therefore unable to supply glucose to the blood.[19]  Thus exercise during delayed GE will cause a super-reduction of venous intra-portal sugar, (my blood glucose level went down 20 mg/dL (n=9 / S.D. =2).  A further decrease in blood sugar of 5 mg/dL (a 25 mg/dL reduction) would cause a sub-physiologic level, such that it would produce a gluconeogenic counter-regulation.

Orexin-A activates the DMNV neurons, followed by an increase of the vagal tone, thereby stimulating gastric antral motility, (see Figure 5).  2-DG stimulates the glucoprivic receptors in the LHA, which in turn initiate and sustain the vagus mediated excitation of gastric function.  Orexin-A-positive neurons in the LHA project to the DMNV.  Orexin-A changes the GI motor pattern from interdigestive to postprandial. [20]

IBS is consistent with alteration related to increased tonic firing of the Locus Coeruleus (LC).  IBS patients showed evidence for increased noradrenergic activity consistent with downregulation of presynaptic inhibitory alpha-2 adrenergic receptors.  A proposed neurobiological model of IBS is upregulation of central arousal circuits involving noradrenergic (NE) signaling.  Alterations in NE pathways originating in the LC of the dorsal pons are implicated in IBS pathophysiology.  Enhanced perception of visceral signals may involve compromised ability to engage endogenous (descending) NE antinocicpetive mechanisms.  NE released from ascending fibers has the highest affinity for alpha-2 receptors, and are predominantly presynaptic, suggesting increased NE release.  Relative regional glucose metabolism, an index of local brain activity, decreased and IBS patients showed increased central NE release, as indexed by smaller reductions (increases) in brain metabolism.[21]  This is the equivalent of increased glucose that is described in the figure above where the increased glucose decreases secretion of LHA/orexin A, not causing DMNV activation.  To induce hypoglycemia, insulin was administered to test animals, which increased LHA tissue  orexin-A protein levels.  Hypoglycemic orexin-a accretion implicates LC neurons in the regulation of these neurotransmitters in the hypothalamus during hypoglycemia.

One gastrointestinal condition that often accompanies migraine is gastric stasis, also called gastroparesis, is defined as delayed emptying of the stomach in the absence of mechanical obstruction.[22]  Dopamine antagonists are indicated for treatment of nausea or psychosis and have an established role in the treatment of migraine.  Neuroleptics, including antipsychotics, act as antagonists at the dopamine DA2 receptor type.  Recent developments suggest that dopamine is particularly important in chronic pain and can be used in the treatment of migraine headache.  Atypical dopamine antagonists are antagonists for DA2 receptors which are widely expressed in areas of the brain thought to be important in migraine, such as the hypothalamus.[23]


The Traction Procedure basically involves 1) drinking coffee, 2) exercising, 3)using the cervical traction for 5 minutes, 4) taking an atypical neuroleptic/anti-psychotic, as a prerequisite.  One drinks coffee to decrease blood sugar, which activates norepinephrine (NE) at the Locus Coeruleus—causing orexin-A secretion from the lateral hypothalamic area.  The decrease in blood sugar, causing an increase in orexin-A secretion in the LHA, can be blocked by 6-OHDA (a selective catecholaminergic neurotoxin) at the caudal fourth ventricle—near the Locus Coeruleus.[24]  Therefore, the Locus Coeruleus secretion of NE caused by IBS pain (acting at alpha 2A receptors), can be beneficial to LHA/orexin-A secretion—to block the pain (at both the trigeminocervical complex(VC1-3 ) and the LC alpha 2A receptors).  In other words,  VC1-3 increased pain causes increased orexin-A secretion to block the trigeminal pain, which also projects to the DMNV, to cause gastric emptying and proximal colon contraction.  I feel that palpable pain in the proximal colon is causing decreased proximal colon stretch.  Proximal colon stretch causes decreased gastric emptying in experimental studies.  A palpable pain which supports the theory that decreased blood sugar activates the LC, occurs at the end of the exercise period, when one yawns as a signal to begin cervical traction.  Yawning behavior is associated with LC/NE neurons which are involved in the arousal response.[25]  This paper seems to be more cohesive with more detailed descriptions of putative pathways that would allow the Traction Procedure to function.  


[1] Camilleri M, “Peripheral mechanisms in irritable bowel syndrome,” 2012, N Engl J Med; 367: 1626- 35.

[2] Balestra et al., “Colonic mucosal mediators from patients with irritable bowel syndrome excite enteric cholinergic motor neurons,” 2012, Neurogastroenterol Motil; 24: 1118-e570.

[3] Haugen et al., “Differential signal pathway activation and 5-HT function: the role of gut enterochromaffin cells as oxygen sensors,” Am J Physiol Gastrointest Liver Physiol, 2012; 303: G1164-73.

[4] Buhner et al., “Submucous rather than myenteric neurons are activated by mucosal biopsy supernatants from ibs patients.: Neurogastroenterol Motil, 2012; 24(12): 1134-e572.

[5] Martinez et al., “Proximal colon distension induces Fos expression in the brain and inhibits gastric emptying through capsaicin-sensitive pathways in conscious rats,” 2006, Brain Res; 1086: 168-80.

[6] Capsaicin-sensitive vagal afferent neurons contribute to the detection of pathogenic bacterial colonization in the gut,”J Neuroimmunol 2013 Mar 4 [Epub ahead of print}.

[7] Holmes GM, ‘Upper gastrointestinal dysmotility after spinal cord injury: is diminished vagal sensory processing one culprit?” 2012, Front Physiol; 3:277.

[8] Pan et al., “Clinical response and autonomic modulation as seen in heart rate variability in mechanical intermittent cervical traction: a pilot study,” 2012, J Rehab Med; 44(3)):229-34.

[9] Yan J., Ogino K, Hitomi J, “The terminal insertional segments and communications of the vertebral nerve in the human cervical region,” 2009, Surg Radiol Anat; 31(3): 165-71.

[10] Rennie et al., “The sinuvertebral nerves at the craniovertebral junction: A microdissection study,” 2012, Clinical Anatomy; 00: 1-10.

[11] Holland et al., “ Modulation of nociceptive dural input to the trigeminal nucleus caudalis via activation of the orexin 1 receptor in the rat.”Eur J Neurosci, 2006; 24: 2825-33.

[12] Goadsby PJ , “pathophysiology of Migraine” Ann Indian Acad Neurol, 2012; 15: s15-s22.

[13] Sadeghi et al., “Involvement of orexin-1 receptors in the ventral tegmental area and the nucleus accumbens in antinociception induced by lateral hypothalamus stimulation in rats.” Pharmacol Biochem Behavior, 2013;{Epub ahead of Print].

[14] Nozu et al., “Endogenous orexin-A in the brain mediates 2-deoxy-D-glucose induced stimulation of gastric motility in freely moving conscious rats.”J Gastroenterol 2012 ; 47: 404-11.

[15] Johnston KL, Clifford MN, Morgan LM, “Coffee acutely modifies gastrointestinal hormone secretion and glucose tolerance in humans:glycemic effects of chlorogenic acid and caffeine,” Am J Clin Nutr, 2003:78(4):728-33.

[16] Bolton P, Budgell B, Kimpton A, “Influence of innocuous cervical vertebral movement on the efferent innervations of the adrenal gland in the rat.” Auton Neurosci, 2008; 124: 103-11.

[17] Pencek et al., “Portal vein caffeine infusion enhances het hepatic glucose uptake during a glucose load in conscious dogs,” 2004, J Nutr ; 134(11): 3042-6.

[18] Arion et al., “Chlorogenic acid and hydroxynitrobenzaldehyde: new inhibitors of hepatic glucose 6-phosphatase,” Arch Biochem Biophys, 1997; 339(2): 315-22.

[19] Nelson DL and Cox MM (2008) Lehninger Principles of Biochemistry, 5th Edition: New York: W.H. Freeman.                                                                        

[20] Berman et al., “Evidence for alterations in central noradrenergic signaling in ibs,” Neuroimage, 2012; 63: 1854-63.


[22] Marmura MJ, “Use of Dopamine antagonists in treatment of migraine,”  Current Treatment Options in Neurology, 2012; 14: 27-34.

[23] Aurora et al., “Gastric stasis in migraineurs; etiology, characteristic, and clinical and therapeutic implications,” Cephalalgia, 2013; {Epub before print].

[24] Gujar et al, “Hypoglycemia differentially regulates hypothalamic glucoregulatory neurotransmitter gene and protein expression: role of caudal dorsomedial hindbrain catecholaminergic input,” Neuropeptides, 2013: [Epub before print].

[25] Kubota et al., “Corticotropin-releasing factor antagonist reduces activation of noradrenalin and serotonin neurons in the locus coeruleus and dorsal raphe in the arousal response accompanied by yawning behavior in rats.” Neurosci Res, 2012; 72: 316-22.

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A PDF file with all five Figures will be provided if you give me your e-mail adress either by a private message or making a comment and including your e- mail adress in your profile.  The Figures may help you understand this article.

  • Report

A brief synopsis of this article in layman’s terms is that one drinks coffee, exercises and takes a Dopamine type 2 receptor blocking prescription/ neuroleptic as a pre-requisite for the cervical traction therapy to function as a treatment for gastroparesis/ gastric stasis.  The traction therapy produces a stretch of the vertebral tendons and ligaments such that the intra-vertebral distance of the cervical bones is increased by about a millimeter.  The traction procedure produces a cervicogenic headache which causes the hypothalamus to secrete a neuropeptide called orexin-A (related to the word anorexia where “orexia” means hunger).  The orexin-A acts at the motor-neuron nucleus of the vagal system (which opposes the adrenal system that produces excitatory responses such as the “fight or flight” response) causing proximal colon motility and is also associated with gastric emptying.  A large bowel movement is usually produced as a result of the procedure.

  • Report

My analysis was praised by the Program Director of the NCCAM (National Center for Complementary and Alternative Medicine) at the NIH (National Institute of Health), as "an interesting theory related to possible effects of cervical traction on gastroparesis, parts of which could be tested."

  • Report

What was determined from the last entry was that cervicogenic headaches caused orexinergic receptors to project to DMVN causing gastric emptying, whether caused by Traction therapy or by spontaneous CG headaches (to block colon pain causing decreased blood glucose brain metabolism and brain activity) via CG headache causing OX-1 (orexinergic receptor type 1) activation.  I.E.  decreased blood sugar (as measured by a blood glucose meter) causes CG headaches that together with Traction causing more CG pain, causes gastric emptying.  With gastric emptying there is an increase in blood sugar causing decreased CG headace, (I have always felt decreased CG headache after traction, together with a bowel movement).  I only have two measurements before and after traction, but on both occations my blood sugar went up 41 and 79 g/dL glucose (associated with gastric emptying as data would indicate inconclusively).  Also, I started taking Garcinia Cambogia to decrease my blood sugar which has become pre-diabetic (111 g/dL) as of last fasting metabolic panel lab test, which works besides other ways as an over the counter Glucophage, to reduce blood sugar.  This pill should help increase transverse colon motility of and by itself.[1]

[1][1] Ketrija Touw et al, “ Altered calcium signaling in colonic smooth muscle of type 1 diabetic mice,”  Am J Physiol Gastrointest Liver Physiol; 302: G66–G76, 2012.


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