Related Experiment Video
Updated: Nov 7, 2025
07:39
Assessment of Nerve Injury-Induced Mechanical Hypersensitivity in Rats Using an Orofacial Operant Pain Assay
Published on: July 26, 2022
3.9K
An orbitofrontal cortex to midbrain projection modulates hypersensitivity after peripheral nerve injury
Junting Huang1, Zizhen Zhang2, Eder Gambeta2
1Department of Anatomy and Neurobiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510080, China; Department of Physiology and Pharmacology, Hotchkiss Brain Institute, Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada.
Cell Reports
|April 28, 2021
Summary
Activating specific neurons in the ventrolateral orbitofrontal cortex (vlOFC) alleviates neuropathic pain symptoms in mice. This research uncovers a key brain circuit for modulating pain hypersensitivity.
Area of Science:
- Neuroscience
- Pain Research
- Computational Neuroscience
Background:
- Neuropathic pain is a severe condition with limited treatment options.
- The neural circuits underlying pain processing and regulation are not fully understood.
- Understanding these circuits is crucial for developing effective pain therapies.
Purpose of the Study:
- To investigate the role of ventrolateral orbitofrontal cortex (vlOFC) neurons in neuropathic pain.
- To identify specific neural pathways involved in pain modulation.
- To explore potential therapeutic targets for neuropathic pain.
Main Methods:
- Utilized neuronal tracing, optogenetics, and chemogenetics in a mouse model of neuropathic pain (spared nerve injury).
- Performed electrophysiological recordings and behavioral assessments to measure pain responses.
- Investigated the connectivity between vlOFC, ventromedial thalamus (VM), and posterior ventrolateral periaqueductal gray (vlPAG).
Main Results:
- Activation of layer 5 pyramidal neurons in the vlOFC significantly reduced mechanical and thermal hypersensitivity and cold allodynia.
- Identified projections from vlOFC to vlPAG and inputs from VM to vlOFC.
- Optogenetic and chemogenetic activation of vlOFC-vlPAG and VM-vlOFC circuits effectively inhibited pain hypersensitivity.
Conclusions:
- The study reveals a novel modulatory role for the vlOFC in processing hypersensitive nociception.
- The vlOFC-vlPAG circuit is identified as a key pathway for inhibiting neuropathic pain.
- These findings provide new insights into brain mechanisms of pain control and potential therapeutic strategies.
Related Concept Videos
01:33Somatosensation
41.5K
The somatosensory system relays sensory information from the skin, mucous membranes, limbs, and joints. Somatosensation is more familiarly known as the sense of touch. A typical somatosensory pathway includes three types of long neurons: primary, secondary, and tertiary. Primary neurons have cell bodies located near the spinal cord in groups of neurons called dorsal root ganglia. The sensory neurons of ganglia innervate designated areas of skin called dermatomes.
41.5K
01:44Nociception
31.7K
Nociception—the ability to feel pain—is essential for an organism’s survival and overall well-being. Noxious stimuli such as piercing pain from a sharp object, heat from an open flame, or contact with corrosive chemicals are first detected by sensory receptors, called nociceptors, located on nerve endings. Nociceptors express ion channels that convert noxious stimuli into electrical signals. When these signals reach the brain via sensory neurons, they are perceived as pain.
31.7K
01:28Major Somatic Sensory Pathways
1.6K
Sensory impulses related to touch, pressure, vibration, and proprioception from various body parts, such as the limbs, trunk, neck, and posterior head, travel to the cerebral cortex through the posterior column-medial lemniscus pathway. The pathway’s name derives from the two white-matter tracts that convey the impulses: the spinal cord's posterior column and the brainstem's medial lemniscus. First-order sensory neurons extend their axons into the spinal cord, forming the...
1.6K
01:25Olfaction
46.6K
The sense of smell is achieved through the activities of the olfactory system. It starts when an airborne odorant enters the nasal cavity and reaches olfactory epithelium (OE). The OE is protected by a thin layer of mucus, which also serves the purpose of dissolving more complex compounds into simpler chemical odorants. The size of the OE and the density of sensory neurons varies among species; in humans, the OE is only about 9-10 cm2.
The olfactory receptors are embedded in the cilia of the...
The olfactory receptors are embedded in the cilia of the...
46.6K
01:24Somatosensory, Motor, and Association Cortex
1.4K
The somatosensory cortex in the parietal lobes is crucial for interpreting sensory data such as touch, temperature, and proprioception. The somatosensory cortex, situated in the parietal lobes, plays a vital role in interpreting sensory information like touch, temperature, and proprioception—awareness of body position. This specialized brain region features an organized structure wherein neurons at the top primarily process sensations originating from the lower body. In contrast, those at...
1.4K
01:21Association Areas of the Cortex
7.4K
Association areas are regions of the cerebral cortex that do not have a specific sensory or motor function. Instead, they integrate and interpret information from various sources to enable higher cognitive processes such as memory, learning, and decision-making. Some key association areas include the following:
Prefrontal Association Area: This area is located in the frontal lobe and is involved in planning, decision-making, and moderating social behavior. It connects with primary motor areas,...
Prefrontal Association Area: This area is located in the frontal lobe and is involved in planning, decision-making, and moderating social behavior. It connects with primary motor areas,...
7.4K