Drug Management of Visceral Pain: Concepts from Basic Research

Abstract

Visceral pain is experienced by 40% of the population, and 28% of cancer patients suffer from pain arising from intra- abdominal metastasis or from treatment. Neuroanatomy of visceral nociception and neurotransmitters, receptors, and ion channels that modulate visceral pain are qualitatively or quantitatively different from those that modulate somatic and neuropathic pain. Visceral pain should be recognized as distinct pain phenotype. TRPV1, Na 1.8, and ASIC3 ion channels and peripheral kappa opioid receptors are important mediators of visceral pain. Mu agonists, gabapentinoids, and GABAB agonists reduce pain by binding to central receptors and channels. Combinations of analgesics and adjuvants in animal models have supra-additive antinociception and should be considered in clinical trials. This paper will discuss the neuroanatomy, receptors, ion channels, and neurotransmitters important to visceral pain and provide a basic science rationale for analgesic trials and management.

Use of non-opioid analgesics as adjuvants to opioid analgesia for cancer pain management in an inpatient palliative unit: does this improve pain control and reduce opioid requirements?

“…Previous studies evaluating the use of adjuvant analgesics in the cancer population have focused on the treatment of neuropathic pain [17]. Our study is unique in examining the use of adjuvants in all cancer patients.…”

“…Gabapentinoids are known to reduce bone and visceral pain [14][15][16][17], and there is evidence that cancerinduced bone pain has a neuropathic mechanisms [18][19][20][21][22][23]. Amitriptyline has been shown to improve neuropathic pain and reduces opioid dose requirements in animal models [24][25][26][27].…”

Protease-Activated Receptors as Therapeutic Targets in Visceral Pain

“…Visceral pain is related to the innervation of the organ by sensory neurons expressing nociceptors. The extrinsic primary afferent innervation of the viscera serves both efferent and afferent functions, but the major function of those neurons is to transfer information from the viscera to the central nervous system [2]. Both vagal and spinal afferent nerve fibers transmit sensory information from the viscera to the central nervous system [2].…”

“…The extrinsic primary afferent innervation of the viscera serves both efferent and afferent functions, but the major function of those neurons is to transfer information from the viscera to the central nervous system [2]. Both vagal and spinal afferent nerve fibers transmit sensory information from the viscera to the central nervous system [2]. Terminal receptors of visceral afferents are located in the mucosa, muscle and serosa of tissues, where they respond to chemical and mechanical stimuli [3].…”

Antinociceptive effect of botulinum toxin type A on experimental abdominal pain

“…Unlike acute forms of visceral pain, chronic visceral pain might be refractory to the listed drugs because of short duration of action, variable effectiveness, and unwanted side effects (Davis, 2012). Thus, there is a need for new therapeutic options with better effectiveness, longer duration of action and acceptable tolerability.…”