Visceral pain

Visceral pain occurs in organs and tissues of the thoracic and abdominal cavities. It may be caused by several factors, including  

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Visceral pain involves injury to nerves on internal organs (e.g., intestines or liver) and can present as diffuse, poorly differentiated, and often referred pain. Acute pain should be treated aggressively, even before the diagnosis is established, except in conditions of head or abdominal injury where pain may assist in the differential diagnosis. 

Distinguish between cutaneous pain and deep visceral pain... 

Pain receptors also influence the medullary respiratory center. Pain may cause a reflex increase in ventilation in the form of a "gasp." Somatic pain typically causes hyperpnea and visceral pain typically causes apnea, or decreased ventilation. 

The predominant adverse effect of clinical use of capsaicin is the burning sensation it produces. Many find it intolerable, and withdrawal rates from clinical studies have been reported as 30% or higher (Szallasi and Blumberg 1999). Excessive ingestion of chili peppers can cause visceral pain, increased peristalsis and diarrhea (Gruenwald 1998). Excessive external application can cause blister and ulcer formation. Very high doses can cause a serious hypothermia. 

Chemical stimuli also underlie pain secondary to inflammation or ischemia (angina pectoris, myocardial infarction), or the intense pain that occurs during overdistention or spasmodic contraction of smooth muscle abdominal organs, and that may be maintained by local anoxemia developing in the area of spasm (visceral pain). 

Acetaminophen (paracetamol) has good analgesic efficacy in toothaches and headaches, but is of little use in inflammatory and visceral pain. Its mechanism of action remains unclear. It can be administered orally or in the form of rectal suppositories (single dose,... 

Recent data also indicate that peripheral NMDA receptors are involved in inflammatory somatic and visceral pain (Teem et al. 2001). Peripheral glutamate receptors are associated with unmyelinated axons (Carlton et al. 1995), and the number of somatic sensory axons containing ionotropic glutamate receptors... 

Colic. Pertaining to the colon acute abdominal pain characteristically, intermittent visceral pain with fluctuations corresponding to smooth muscle peristalsis. Conjunctivitis. Inflammation of the delicate membrane that lines the eyelids and covers the exposed surface of the sclera (conjunctiva), generally consisting of conjunctival hyperemia associated with a discharge. 

Visceral pain e.g. myocardial infraction, pleurisy, vascular occlusion, renal and biliary colic. 

Analgesic action Salicylates relieve pain by both central and peripheral action. The site of action of central analgesia seems to be the hypothalamus. It does not have cortical action on the reaction component of the pain but raises the threshold to pain perception. Unlike morphine, they do not produce sedation and there is no drug tolerance or dependence and are not effective against visceral pain. 

There are two major classes of pain medications, nonopioids and opioids. The nonopioids used to treat mild pain include agents such as acetaminophen, both steroid and nonsteroidal antiinflammatory drugs (NSAIDs), and acetylsalicylic acid. Anticonvulsants suppress neuronal firing and are also helpful in neuropathic pain. Antiinflammatory agents (e.g., NSAIDs or corticosteroids) may be particularly helpful when bony involvement occurs and are often used for low-intensity pain. Steroids decrease inflammatory edema and are useful in cases of nerve and spinal cord compression, lymphedema, visceral pain caused by organ enlargement, and bone pain. Finally, short-term corticosteroid therapy may also produce euphoria (thus ameliorating less severe depressions) as well as reverse anorexia. 

A3 receptors. These are also known collectively as purine PI receptors. There are two other classes of purine receptors, P2X and P2Y, which are thought to be involved in nociception and especially visceral pain. The ligand for these receptors is ATP. The A1 receptor is coupled to the inhibitory Gi protein and the A2 receptor to the stimulatory Gs protein, and respectively inhibit or activate adenylyl cyclase, while the A3 receptor mediates G protein-dependent activation of phospholipase C. 

Compounds with moderate p-affinities are very potent in a variety of pain models in mice and rats. In addition to antinociceptive efficacy in models of acute pain (tail flick, writhing) these compounds inhibit acute and persistent inflammatory pain (Randall Selitto, formalin test). Furthermore, they show strong inhibition of acute visceral pain (colorectal distension) and of tactile and cold allodynia in models of neuropathic pain (spinal nerve ligation (Chung), chronic constriction injury (Bennett)). The data suggest these compounds to be potential candidates for the management of clinical pain indications. Somatic and visceral pain with and without inflammatory conditions as well as neuropathic pain might be addressed with this approach. 

MRZ-2/576 has been demonstrated to cross the blood -brain barrier rapidly and to function centrally as a glycineB antagonist after systemic administration of doses within the relevant antinociceptive dose range. However, the compound is only short-acting within the CNS because of a relatively short half-life within this compartment (Parsons et al., 1997). The compound has antinociceptive properties and shows exceptionally good efficacy in a visceral pain model (McClean et al., 1998 Olivar et al., 1999). 

Lagerquist, B., Sylven, C., Beermann, B., Helmius, G., Waldenstrom, A. Intracoronary adenosine causes angina pectoris like pain - an inquiry into the nature of visceral pain, Cardiovasc. Res. 1990, 24, 609-613. 

The antinociceptive effect of CGRP(8-37) was observed in different pain types of such as abdominal pain (p-phenylquinone induced writhing, Saxen et al., 1994 acetic acid-induced writhing, Friese et al., 1997), visceral pain (colorectal distension model, Plourde et al., 1997), burn pain (heat-induced hyperalgesia Lofgren etal., 1997), and... 

Assuming that we can apply these results to the human situation, CGRP1 antagonists may also be effective for treatment of chronic inflammatory and visceral pain but not for acute pain. A thorough evaluation of this receptor in neuropathic pain is still missing. 

Friese, N., Diop, L., Chevalier, E., Angel, F., Riviere, P.J.M., Dahl, S.G. Involvement of prostaglandins and CGRP-dependent sensory afferents in peritoneal irritation-induced visceral pain, Reg. peptides 1997, 70, 1-7. 

Animal models of nociception can be divided according to the therapeutic indication Acute Pain, Migraine Pain, Inflammatory Pain, Visceral Pain, Neuropathic Pain. Different degrees of chronification (up to weeks in neuropathic pain models) and different stimuli (mechanical, thermal, chemical, electrical) are used depending on the experimental question. In most cases a nociceptive threshold (e g. withdrawal latency of a paw) is determined. Sometimes, nociceptive intensities are determined e.g. in order to quantify hyperalgesia. 

Pain research is a traditional and well established field within the pharmaceutical industry. Beginning with the isolation of morphine in a small pharmacy by Adam Serturner (1806), the next major breakthrough in pain treatment was achieved by the synthesis of acetylsalicylic acid by Felix Hoffmann in the Bayer Laboratories in Wuppertal (1897). Further outstanding contributions by the pharmaceutical industry were the first fully synthetic opioids pethidine (1939) and methadone (1946). Continued efforts up to now have resulted in many potent and clinically accepted analgesics with reasonable side effects and covering nearly all facets of pain treatment. However, pain treatment is far from being satisfactory in respect to more complex pain states, e.g. neuropathy, visceral pain or migraine. 

Riviere PJ. Peripheral kappa-opioid agonists for visceral pain. Br J Pharmacol. 2004 141 1331-1334. 

Animal and human clinical studies demonstrate that both endogenous and exogenous opioids can also produce opioid-mediated analgesia at sites outside the CNS. Pain associated with inflammation seems especially sensitive to these peripheral opioid actions. The identification of functional p receptors on the peripheral terminals of sensory neurons supports this hypothesis. Furthermore, activation of peripheral preceptors results in a decrease in sensory neuron activity and transmitter release. Peripheral administration of opioids, eg, into the knees of patients undergoing arthroscopic knee surgery, has shown some clinical benefit. If they can be developed, opioids selective for a peripheral site would be useful adjuncts in the treatment of inflammatory pain (see Ion Channels Novel Analgesics). Moreover, new peripherally acting dynorphins may provide a novel means to treat visceral pain. 

Aspirin is employed for mild to moderate pain of varied origin but is not effective for severe visceral pain. Aspirin and other NSAIDs have been combined with opioid analgesics for treatment of cancer pain, where their anti-inflammatory effects act synergistically with the opioids to enhance analgesia. High-dose salicylates are effective for treatment of rheumatic fever, rheumatoid arthritis, and other inflammatory joint conditions. 

Fig. 1. Roles of the CeA and BLA in somatic and visceral pain-induced aversion. Please see the text for details.

Deyama, S., Katayama, T., Kondoh, N., Nakagawa, T., Kaneko, S., Yamaguchi, T., Yoshioka, M., and Minami, M. (2009). Role of enhanced noradrenergic transmission within the ventral bed nucleus of the stria terminalis in visceral pain-induced aversion in rats. Behav. Brain Res. 197, 279-283. 

Tanimoto, S., Nakagawa, T., Yamauchi, Y., Minami, M., and Satoh, M. (2003). Differential contributions of the basolateral and central nuclei of the amygdala in the negative affective component of chemical somatic and visceral pains in rats. Eur.J. Neurosci. 18, 2343-2350. 

Wang, H. C.j Chai, S. C., Wu, Y. S., and Wang, C. C. (2007). Does the medial thalamus play a role in the negative affective component of visceral pain in rats Neurosci. Lett. 420, 80—84. 

Wang, X., Miyares, R. L., and Ahem, G. P. (2005). Oleoylethanolamide excites vagal sensory neurones, induces visceral pain and reduces short-term food intake in mice via capsaicin receptor TRPV1. J. Physiol. 564, 541-547. 

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