References

Somatic and visceral primary afferents in the lower thoracic dorsal root ganglia of the cat. J Comp Neurol 1984 228(3) 422-431. 2. Chandler MJ, Zhang J, Foreman RD. Vagal, sympathetic and somatic sensory inputs to upper cervical (C1-C3) spinothalamic tract neurons in monkeys. J Neurophysiol 1996 76(4) 2555-2567. 3. Randich A, Gebhart GF. Vagal afferent modulation of nociception. Brain Res Brain Res Rev 1992 17(2) 77-99. 4. Cervero F. Visceral pain-central...

Referred Hyperalgesia

As already discussed above, most forms of visceral pain produce an increased tenderness of remote and superficial areas of the body known as referred visceral hyperalgesia (22). The fact that referred hyperalgesia appears to originate from otherwise healthy tissues strongly suggests that their locus of origin is in the CNS rather than in the periphery. The conceptual framework underpinning the central organization of visceral hyperalgesia originates from James MacKenzie, who in his classical...

Functional Gut Disorders

More than half of the patients in a gastroenterological clinic complain of abdominal symptoms, without demonstrable cause by conventional diagnostic tests. In the absence of positive findings, unexplained abdominal symptoms have been categorized as functional gastrointestinal disorders, and several syndromes, such as noncardiac chest pain, functional dyspepsia, and the irritable bowel syndrome (IBS), have been defined. Non-cardiac chest pain refers to patients with thoracic symptoms without...

Is Hyperalgesia Limited to the Gut in Irritable Bowel Syndrome

The first studies to investigate visceral sensitivity in IBS concluded that enhanced sensitivity in IBS was limited to the gut (43-46). Interestingly, two prior studies have examined cutaneous pain in IBS patients using electrocutaneous stimulation (43,44). In one study, 13 patients with Crohn's disease, 13 control subjects, and 12 patients with IBS had electrodes positioned on the Figure 3 IBS patients' and normal control subjects' M-VAS pain Intensity ratings of rectal distension pressures of...

Psychological Modulation of Pain Processing

Perception of visceral sensation is mediated at a cortical level and is therefore influenced by cognitive mechanisms such as stress, attention, and anxiety. Attention to gastrointestinal (GI) stimuli has been shown to increase their perception (45), and there is evidence that psychological mechanisms such as anxiety play a role in modulating visceral sensory perception (46). Stress can be defined as an intrinsic or extrinsic disturbing force that threatens to disturb the homeostasis of an...

The Biopsychosocial Continuum

The biopsychosocial model (5) proposes that illness and disease result not from a single (biological) etiology, but from simultaneously interacting systems at the cellular, tissue, organism, interpersonal, and environmental level. Furthermore, psychosocial factors have direct physiological and pathological consequences and vice versa. Finally, it is the unique contributions of both psychosocial and pathophysiological factors that determine the nature of the illness or disease and its severity...

The Bladder

The most common form of bladder pain in the clinic is that caused by infection, resulting in cystitis, although overdistension of the bladder in acute urinary retention is also very painful. These two mechanisms have been employed in the design of rodent models of bladder pain, using direct distension of the bladder, or instillation of chemical or infectious agents. Environmental stressors have also been used, as stress is known to exacerbate symptoms in human disease. Ness et al. demonstrated...

Sensory Neurons And Gi Hypersensitivity

Studies of the possible mechanisms underlying FBDs have shown that abdominal hypersensi-tivity is an important factor in noncardiac chest pain, functional dyspepsia, and IBS (see Chapters II 3, II 6, II 7, II 9 and II 10). The concept that primary afferents are a relevant target for treating abdominal pain implies that these neurons are sensitized in states of hyper-algesia or undergo other functional changes that are relevant to hypersensitivity. Indeed, most extrinsic afferents innervating...

Section Iv Clinical Syndromes Pathophysiology Diagnosis And Management

Irritable Bowel Syndrome and Functional Abdominal Pain Syndromes Pathophysiology 341 Andrew W. DuPont and Pankaj Jay Pasricha Introduction and Nature of the Problem 341 Is Pain Secondary to Motility Abnormalities in IBS 342 Is Pain Secondary to Disturbances in Sensory Processing (Visceral Hypersensitivity) 343 Visceral Hypersensitivity Central or Peripheral 345 Etiopathogenesis of Visceral Hypersensitivity 350 Conclusions . . . . 353 References 353 Irritable Bowel Syndrome and Functional...

Referred Pain Phenomena In The Clinical Context Referred Pain Hyperalgesia

Referral of pain to distant structures is a typical feature of visceral nociception 2,8 . It is only in the very first episode, or early phases of the first episode, in fact, that pain symptoms from internal organs are perceived in a common site for all viscera i.e., usually along the midline, in the thorax or abdomen, anteriorly, or posteriorly . At this stage, the symptom is a vague and poorly defined sensation, accompanied by marked neurovegetative signs and emotional reactions the so-called...

Modulation of Pain by the Hypothalamic PituitaryAdrenal Axis

Mast Cell Crh Stress

The hypothalamus is sited at the base of the brain around the third ventricle and above the pituitary stalk, which leads down to the pituitary itself, carrying the hypophyseal portal blood supply. It contains vital centers for functions including appetite, thirst, thermal regulation, and the sleep cycle, and acts as an integrator of many neuroendocrine inputs to control the release of pituitary hormone-releasing factors. Amongst other important influences, it plays a role in the circadian...

CRF Antagonists

In addition to the mimicry in the responses triggered by stress and central injection of CRF, the evidence for a role of brain CRF-signaling pathways in the stress response came from studies using CRF receptor antagonists injected into the cerebrospinal fluid. Among the specific nonselective CRF1 CRF2 antagonists are a-helical CRF9-41 88 , D-Phe12CRF12-41 89 , and the recently developed, more potent and long acting peptides, astressin 90,91 and astressin B 92 . The potential therapeutic...

Section Ii The Neurobiology And Psychobiology Of Chronic Visceral Pain

Overview of Pain and Sensitization 17 Michael S. Gold What is Pain 17 Pain Terminology 18 Summary and Conclusions 27 References 27 4. Neuroanatomy of Visceral Pain Pathways and Processes 33 Elie D. Al-Chaer and William D. Willis Peripheral Pathways 33 Central Pathways 34 Representation of Visceral Sensation in the Brain 38 References 39 5. The Neurobiology of Visceral Nociceptors 45 Stuart M. Brierley and L. Ashley Blackshaw Introduction 45 Irritable Bowel Syndrome 45 Sensory Innervation of...

The Small Intestine

Tunel Short Bowel Syndrome Rats

Distension and resection 26 of the ileum, jejunum including traction of the mesentery 27 , and duodenum has been described in rodents for the purposes of this review, we shall Figure 2 Acetic acid produces gastric ulcers in the rat. Kissing ulcers A , induced in a rat three days after intraluminal application of 60 acetic acid. Arrows indicate round ulcers on the posterior and anterior walls. Using a different method injection of 20 acetic acid into the stomach wall , the visceromotor response...

Visceral Hypersensitivity Historical Background

Some reports in the 1970s described disturbances of gut perception in patients with the irritable bowel and related syndromes, but these studies remained largely ignored. These classic observations were later reconfirmed and expanded, clearly showing a colonic and rectal hypersensitivity in these patients. Further studies tested whether symptoms after meal ingestion in patients with functional dyspepsia were due to a sort of gastric rigidity, that is, to altered compliance and an abnormal...

Sensory Innervation Of The Gastrointestinal Tract

The sensory, or afferent, innervation of the gastrointestinal tract mediates sensations from the gut and initiates reflex control of digestive function. The afferent fibers innervating the gastrointestinal tract follow two main anatomical branches, the vagal pathway and the spinal pathway. Vagal afferents have axons which project directly into the brainstem to the nucleus tractus solitarius whereas their cell bodies are located in the nodose ganglia. Vagal afferents are important in the sensory...

Pathways in the Dorsal Funiculus

The dorsal funiculus, also referred to as the dorsal column in animals or the posterior column in man, contains collateral branches of primary afferent fibers that ascend from the dorsal root entry level all the way to the medulla 31 . In addition, it contains the ascending axons of tract cells of the dorsal horn 60-65 . These tract cells form the postsynaptic dorsal column pathway, which along with primary afferent axons, travels in the dorsal column and synapses in the dorsal column nuclei....

Psychophysical Studies Of Visceral Sensation

To determine whether uncontrolled clinical observations are indeed representative of responses evoked by visceral pain rather than a nonspecific characterization of chronic pain, psychophysical studies have been performed using controlled visceral and nonvisceral stimuli in both healthy subjects and those with clinical diagnoses of painful visceral disorders. Visceral stimuli have included chemical, electrical, thermal, and mechanical stimuli 15 . Most studies have not attempted to compare...

Relationships of Temporal Summation of Mechanical Allodynia to Severity of Clinical Pain

Regardless of the exact mechanisms by which temporal summation of allodynia is generated, the phenomenon is likely to be at least part of the basis for CRPS patients' ongoing ''spontaneous'' pain. It has been suggested that temporal summation of A-beta allodynia provides at least part of the basis for ongoing background pain in neuropathic pain patients 17 . This relationship could occur if continuous input from A-beta low threshold afferents evoked in the normal course of mechanical...

Visceral Hypersensitivity

Although FGD patients show marked heterogeneity in their clinical presentation and response to treatment, common features have become apparent, as our knowledge of these disorders has increased. It was documented over 30 years ago by Ritchie that recto-sigmoid balloon distension was perceived as painful at lower volumes in IBS patients than in controls 3 . This heightened pain sensitivity to experimental gut stimulation, a phenomenon known as visceral hypersensitivity, has been repeatedly...

Distension of Hollow Viscera

Gut distension has been widely used to test sensitivity, both in experimental animals and in conscious man. Gastrointestinal distension in healthy subjects induces sensations such as abdominal pressure and fullness, referred to the epigastrium and the paraumbilical region. The type of sensations induced by distension is rather homogeneous from the stomach down to the mid small bowel 5-8 , which indicates that the expression of the gut in response to stimuli, and the discriminative value of...

Evidence for Autonomic Nervous System Dysfunction

A number of studies have addressed the role of the ANS in modulating visceral perception in FGD. Chen and Orr demonstrated enhanced sympathetic dominance to esophageal acid infusion in patients with gastroesophageal reflux disease GERD , which appeared to be secondary to decreased vagal tone in these subjects 121 . During acid infusion, there was a significant decrease in LF band power a measure of sympathetic tone in the control group, which was unchanged in the patient group, whereas the HF...

Viscerovisceral Convergence

Mechanistically, viscerovisceral convergence is similar to viscerosomatic convergence. The extensive divergence of the visceral afferent fibers in the spinal cord results in primary afferents that innervate different viscera converging onto a single dorsal horn neuron 37,52-55 . This may result in stimulation of two viscera exciting the same dorsal horn neuron Fig. 4A or stimulation of one viscus, through interneurons, inhibiting a dorsal horn neuron while stimulation of another organ excites...

The Large Intestine Rectum and Anus

Colorectal distension CRD is the most widely used model of organ distension, and has been characterized in both the rat 6 and the mouse 42,43 . This method reproducibly generates painful responses in both animals and humans as the result of a natural visceral stimulus, and is minimally invasive a balloon or similar device can be inserted anally. Such techniques produce acute pain and can be combined with intracolonic treatment with chemicals that produce insult or inflammation such as acetic...

Differences in Brain Responses to Visceral and Somatic Pain Stimuli

Extensive visceral esophageal balloon distension and somatic contact heat on the midline chest animal and human experimental studies have demonstrated that the perceptual, auto-nomic, and behavioral responses to noxious stimulation of somatic structures differ from those of the viscera 28,29 . These differences have been explained based on the functional neuro-anatomic differences between visceral and somatic pain processing. Experimentally induced aversive visceral sensations in humans are...

Divergence of Visceral Afferents in the Spinal Cord

Nociceptor Afferent Fiber

In addition to the dual innervation of viscera by sensory afferent fibers, the central projection and terminal arborization of these visceral afferent fibers are highly divergent compared to somatic afferents. Somatic afferents project to well-defined regions within the dorsal horn Fig. 2A 22-26 . Small diameter myelinated and unmyelinated fibers, most of which are associated with nociceptors, terminate in the superficial dorsal horn and to a lesser extent in Figure 1 The sensory innervation of...

Neuroanatomy Of Visceral Pain

Celiac Ganglion

Basic science studies have demonstrated that from the level of gross anatomy to the microscopic determination of both peripheral and central afferent terminals, visceral sensory pathways are diffusely organized and distributed diagrammatic summary in Fig. 1 . Rather than mimicking the precise organization of cutaneous sensory afferent pathways, which travel in defined peripheral nerves and extend into a limited number of spinal segmental nerves organized in a unilateral, somatotopic fashion,...

Central Sensitization

Central Sensitization

As mentioned, peripheral injury of primary afferent sensory neurons can be associated with peripheral sensitization. Also, recruitment of previously silent nociceptive neurons can occur which remain active after the injury heals. The increase in nociceptive information arriving at the spinal cord from these peripheral sites can enhance the excitability of dorsal horn neurons, Figure 1 See color insert The potential receptor mechanisms mediating depolarization and sensitization of visceral...

Spinal and Supra Spinal Modulation of Pain Perception

Descending Pain Modulatory System

Working with rats and using simple withdrawal reflexes as pain measures, Reynolds 31 showed that stimulation of a specific region of the midbrain periaqueductal gray PAG inhibited behavioral responses to noxious stimulation, giving rise to the term stimulation produced analgesia.'' Stimulation of these sites inhibited responses of spinal neurons to noxious stimuli suggesting that the brain could modulate spinal activity. The PAG receives direct inputs from the hypothalamus and from the limbic...

Viscerosomatic Inhibition

Patients with IBS or other disorders with visceral hypersensitivity report referred somatic hypersensitivity in the dermatomes where referred pain is perceived. However, outside the area of referred pain, as long as there is not a codiagnosis of another ailment such as fibro-myalgia, patients report normal or hyposensitivity to noxious electric and mechanical somatic stimuli 4,126-131 . In contrast, thermal stimulation is more painful in IBS patients compared to controls, although this...

The Neuroanatomy of Visceral Pain

While Chapter 4 provides a review of the neuroanatomy of visceral pain, a basic understanding is advantageous when considering the models presented here. We therefore begin with a brief overview of the basic afferent innervation of the viscera. The visceral organs are innervated by extrinsic afferent nerves that run alongside the sympathetic and parasympathetic nervous systems, but are not part of these efferent pathways however, they are referred to by the name of the respective autonomic...

Central Pathways

Spinoparabrachial Tract

Upon entering the dorsal horn, visceral afferents terminate in spinal cord laminae I, II, V, and X 11 . Visceral afferents constitute less than 10 of afferent inflow into the spinal cord. This is a relatively small percentage when one considers the large surface area of some organs. Both anatomical and electrophysiological studies have demonstrated viscerosomatic convergence in both the dorsal horn and supraspinal centers 11-15 . There is also evidence of viscero-visceral convergence onto these...

Distensiontension Sensitive Afferents

Afferents within the wall of the gastrointestinal tract that respond broadly to distension or stretch of a region of gut have been extensively characterized. However, to add complexity, these afferents have been described by a variety of names including distension-sensitive, tension-sensitive, stretch-sensitive, muscular afferents, tonic, phasic, and low-threshold, high-threshold and wide dynamic range fibers to name but a few. Recent reviews indicate differences in the signals generated by...

Heat Allodynia and Hyperalgesia in Fibromyalgia Patients

There are pain conditions that, unlike CRPS described above, are characterized by diffuse pains and hyperalgesia over large areas of body. The ability to use the same patients as their own control in establishing hyperalgesia and allodynia is therefore more challenging in these patient populations. An alternative approach is to compare their ratings of experimental heat stimuli to groups of age- and sex-matched control subjects. For example, heat hyperalgesia has been shown to be a prevalent...

Contributors

Al-Chaer Departments of Pediatrics, Neurobiology and Developmental Sciences, Center for Pain Research, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas, U.S.A. Q. Aziz Department of Gastrointestinal Science, University of Manchester, Hope Hospital, Salford, U.K. Fernando Azpiroz Digestive System Research Unit, University Hospital Vall d'Hebron, Autonomous University of Barcelona, Barcelona, Spain Jane C. Ballantyne Department of Anesthesia and...