The Rostral Ventromedial Medulla (RVM) The rostral ventromedial medulla has appeared consistently in nearly all major scientific reviews exploring the physiology of pain in modern medicine. This biological structure is recognized as a major component of the pain modulatory circuitry, exerting its modulatory effects in addition to relaying the modulatory effects from higher brainstem sites. It is a large region of the medulla that includes the midline nucleus raphe magnus (NRM) and portions of the adjacent reticular formation, the nucleus reticularis gigantocellularis pars alpha (GiA) and the nucleus paragigantocellularis lateralis (LPGi) (WeiWei et al., 2021). Efferent projections from the RVM extend bilaterally, have been identified in all levels of the spinal cord, and comprise a major portion of the neurons projecting to the spinal dorsal horn. These neurons have widely collateralized yet lamina-specific projections, with dense bilateral terminations in laminae I, II, and V of the spinal cord dorsal horn. While all of the components of the descending modulatory network are important, the PAG and RVM have been shown to play key roles in the underlying mechanisms of pain modulation. Further, the PAG to RVM projection is critical for the PAG to exert its descending modulatory effect on dorsal horn nociceptive neurons. The RVM exerts its modulatory effect on nociceptive transmission at the spinal level, producing antinociception to painful stimuli. During persistent noxious stimulation, such as during a prolonged inflammatory state, there is continued activation of the descending pain modulatory circuitry and increased neuronal activity in the RVM that results in a progressive enhancement of descending modulation of spinal nociceptive transmission (Bagley & Ingram, 2020). horn, where it has been shown that neighboring neurons are simultaneously under facilitatory and inhibitory control from supraspinal structures. The balance between inhibition and facilitation determines the net effect of descending modulation on nociceptive transmission. Overall, the physiological processing of pain is a complex phenomenon, involving both the peripheral and central nervous systems. Nociceptive information regarding actual or potential tissue injury is transmitted from peripheral nerve endings (nociceptors), via a complex series of ascending pathways, to the brain. Within the brain, the nociceptive signals are further processed in the somatosensory cortex and interpreted as pain. As the ascending nociceptive information passes through the brainstem and reaches the brain, it triggers the activation of a network of brainstem structures and pathways that exert a modulatory effect on nociceptive transmission. The structures involved in pain modulation send neuron projections from the brainstem to the spinal dorsal horn where their modulatory effect alters the transfer of nociceptive information from the primary afferent to the second-order neuron. Thus, the flow of further nociceptive information from the periphery is either inhibited (resulting in less pain) or facilitated (resulting in more pain). abdominal pain. With the help of a local traditional medicine specialist, he was revived and managed for lower abdominal pain thought to have resulted from Elanga’s rigorous farming schedule. He would go on to live pain-free until about 2 weeks ago when he presented in the emergency department of a private clinic in the neighboring Guadalajara district. He presented with a right, lower abdominal pain described on assessment as ‘radiating, throbbing, continuous and stabbing at intervals.’ Elanga, visibly pale and fatigued, described how the pain had started 3 days before presentation accompanied by fainting spells, general body weakness, and vomiting. Pain is worsened by walking or sudden movement of the lower limb and is not managed by any local traditional pain remedy. He denies tingling sensations in the lower limb, brute force,
The first theory in this regard maintained that pain is under the influence of higher areas in the CNS. Early studies confirmed this theory by providing evidence that many supraspinal sites contribute to the control of ascending sensory input by exerting tonic inhibitory control of neurons in the spinal dorsal horn. Further research into the contribution of supraspinal structures to nociceptive modulation showed that the mammalian CNS has several well-defined, supraspinal-organized descending pathways. These pathways form a network of neural systems that modulate the ascending transmission of nociceptive information, with the most well-described being the circuitry mediating the brainstem control of nociceptive transmission at the level of the spinal dorsal horn. The effects of descending modulation are exerted in the spinal dorsal horn on the synapse between the primary afferent and projection neurons or on interneurons that synapse with projection neurons. This synapse in the dorsal horn is the point where nociceptive information is first integrated before being transmitted to higher centers in the CNS (Gamal-Eltrabily et al., 2021). The descending modulatory effect is applied either by inhibiting the release of neurotransmitters from the primary afferent fiber or by inhibiting the function of neurotransmitter receptors on the postsynaptic neuron. Several supraspinal sites are known to contribute to the descending modulation of nociception, either directly (sending projection neurons to the spinal cord) or indirectly (sending projection neurons to other regions in the brainstem that send projections to the spinal cord). These include the PAG, the locus coeruleus (LC), and the rostral ventromedial medulla (RVM) among others. as it concerns pain modulation, there are reasons to agree that the descending modulation of nociception is not wholly inhibitory. A few studies demonstrated time-dependent biphasic properties of the pain modulatory system that can both inhibit and facilitate nociceptive transmission. However, many aspects of the underlying mechanisms of nociceptive modulation and the shift from facilitation to inhibition remain largely unclear. The RVM is one area in the pain modulatory system that puts forth opposing modulatory effects and is a crucial site for balancing Biphasic modulation of pain Judging from the clinical evidence supplied in modern medicine descending modulation. When activating the descending pathways that originate in the RVM, the effect (inhibitory or facilitatory) is dependent on the intensity and nature of the intra- RVM stimulus. Although the circuitry responsible for generating facilitatory and inhibitory modulation may be distinct, an anatomical and neurochemical differentiation of the bimodal modulatory structures has not been determined. However, several studies that used either electrical stimulation or lesions have shown opposing modulatory effects from the different subregions of the RVM. The effects of both descending inhibition and facilitation have been observed during multi-neural recording in the dorsal Case study 2—Elanga’s subsistent farming career Elanga Vera lived as a popular arable farmer in Acapulco, Mexico, contributing a sizeable quota to the Subsistent Agricultural Sector of his local district. Although access to farming modernization was possible, an agile 67 years old Elanga still fancied doing farming the old way. His methods of subsistent agriculture employed crude farming methods that are labor-intensive and less capital-intensive. For the past 35 years, he has consistently formed a large landscape of arable lands year in and years out. Since access to primary healthcare and monitoring is considerably poor in his district, Elanga’s last visit to the Primary Healthcare Center was 7 years ago in a bid to present a reoccurring case of papular skin rashes. About 6 months ago while working on the farm, Elanga reportedly fainted after a complaint of a sharp, throbbing lower
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