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iNature
Visceral pain is one of the most common and annoying forms of chronic pain, but its spread in the spinal cord is still poorly
understood.
On December 29, 2022, Ma Qiufu's research group of Westlake University published an online report entitled "Spinal VGLUT3 lineage neurons drive visceral mechanical allodynia but not sensitized visceromotor reflexes" online in Neuron magazine This study performed focal colorectal distention (fCRD) to drive viscero motor responses (VMRs
).
The study found that spinal cord VGLUT3 neurons mediate visceral dyspain, and its knockout leads to gastrointestinal (GI) inflammation or spinal cord circuitry to inhibit the loss of disgust caused by low-intensity fCRD in mice
.
Importantly, under inflammatory and central desuppressive conditions, these neurons are dispensable for driving sensitized VMRs
.
Anatomically, a subset of VGLUT3 neurons projects to the parabrachial nucleus, whose photoactivation sufficiently produces aversion in mice with gastrointestinal inflammation without affecting VMRs
.
In summary, this study suggests the presence of different spinal cord substrates that transmit visceral sensory messages in pain and emotional dimensions
.
compared to skin pain.
In this study, the researchers aimed to identify the spinal cord matrix that transmits visceral information
.
Over the past decade, tremendous progress
has been made in describing spinal cord neurons that transmit or block pain in the skin.
These studies reveal the presence of different spinal cord substrates that drive exoceptive reflex-defense responses to external threats, and endoceptive self-care responses
to actual physical injuries that produce tension-affective pain.
Because of this circuit-level isolation, the loss
of cutaneous affective pain may not be detectable when measuring first-line reflexive defense responses.
At the same time, despite great clinical significance and unmet medical need, modern genetic and viral tools are rarely used to characterize the spinal cord circuits that transmit visceral sensory information, although electrophysiological, molecular, and behavioral studies have revealed sensitization of spinal cord neurons following visceral inflammation or stress
.
In 1988, Ness and Gebhart introduced two experiments to study pain and disgust caused by colorectal distention (CRD), a stimulus
that produces pain in humans.
One is to measure pain sensation by recording abdominal muscle contraction with electromyography (EMG), called visceral motor responses (VMRs
).
The other is to measure the degree of
disgust through stepwise avoidance learning experiments.
Disgust and distress can also be measured
by two-chamber conditioning avoidance experiments or post-stimulus ultrasound sounding recordings.
While aversive learning and pain vocalizations may better reflect emotional experiences, VMRs have long been used as surrogate tests
to measure visceral pain.
However, VMRs are preserved in brain-debrained animals, while in humans, cortical structures such as the anterior cingulate cortex (ACC) are essential
for the experience of emotional pain and emotional pain.
Consistently, lesions of rat ACC lead to the loss of affective inflammatory visceral pain without affecting sensitized VMRs
.
Conversely, some drugs that block VMRs cannot treat visceral pain in humans, note that anterior cingulate gyrus is in the final stage
of processing emotional messages.
However, until now, it is unclear whether the spinal cord stromal drives affective pain differently with VMRs
.
In this study, the researchers found that the spinal vesicle glutamate transporter 3 (VGLUT3) lineage neurons, marked by transient developmental expression of the VGLUT3 gene, needed to drive low-intensity focal CRD (fCRD) in colitis or central inhibition to inhibit disgust
in mice.
Importantly, VMRs remained intact
in mice that removed these neurons.
In addition, the researchers identified that spinal cholecystokinin (CCK) neurons drive VMRs and harmful fCRD-induced disgust
under infantile conditions.
PB-projected spinal cord VGLUT3 lineage neuronal drive aversion (Image from Neron)
Overall, this study shows that there are different spinal cord circuit-driven sensitized VMRs with visceral pain drawn by emotions, and similar circuits are separated horizontally when
dealing with different dimensions of skin somatosensory information.
Future studies will be directed towards describing a SOM-negative subset
of CCK lineage neurons that transmit harmful visceral mechanical information.
Original link: https://doi.
org/10.
1016/j.
neuron.
2022.
12.
003
—END—
The content is [iNature]
