The team’s discovery, reported Nov. 6 in the journal Science Advances, offers researchers a deeper understanding of the complicated relationship between pain and touch and could offer some insights into chronic pain in humans.
“We’re interested in this because it’s a common human experience,” says McGovern investigator Fan Wang.
Modeling pain relief
Touch-mediated pain relief may begin in the spinal cord, where prior studies have found pain-responsive neurons whose signals are dampened in response to touch. But there have been hints that the brain was involved, too.
Wang says this aspect of the response has been largely unexplored, because it can be hard to monitor the brain’s response to painful stimuli amidst all the other neural activity happening there — particularly when an animal moves.
So while her team knew that mice respond to a potentially painful stimulus on the cheek by wiping their faces with their paws, they couldn’t follow the specific pain response in the animals’ brains to see if that rubbing helped settle it down.
She and her colleagues have found a way around this obstacle. Instead of studying the effects of face-rubbing, they have focused their attention on a subtler form of touch: the gentle vibrations produced by the movement of the animals’ whiskers.
Mice use their whiskers to explore, moving them back and forth in a rhythmic motion known as whisking to feel out their environment. This motion activates touch receptors in the face and sends information to the brain in the form of vibrotactile signals.
The human brain receives the same kind of touch signals when a person shakes their hand as they pull it back from a painfully hot pan — another way we seek touch-mediate pain relief.
Whisking away pain
Wang and her colleagues found that this whisker movement alters the way mice respond to bothersome heat or a poke on the face — both of which usually lead to face rubbing.
In the brain’s somatosensory cortex, where touch and pain signals are processed, the team found signaling changes that seem to underlie this effect.
“The cells that preferentially respond to heat and poking are less frequently activated when the mice are whisking,” Wang says. “They’re less likely to show responses to painful stimuli.”
Even when whisking animals did rub their faces in response to painful stimuli, the team found that neurons in the brain took more time to adopt the firing patterns associated with that rubbing movement.
“When there is a pain stimulation, usually the trajectory the population dynamics quickly moved to wiping. But if you already have whisking, that takes much longer,” Wang says.
Wang notes that even in the fraction of a second before provoked mice begin rubbing their faces, when the animals are relatively still, it can be difficult to sort out which brain signals are related to perceiving heat and poking and which are involved in whisker movement. Her team developed computational tools to disentangle these, and are hoping other neuroscientists will use the new algorithms to make sense of their own data.
Whisking’s effects on pain signaling seem to depend on dedicated touch-processing circuitry that sends tactile information to the somatosensory cortex from a brain region called the ventral posterior thalamus.
When the researchers blocked that pathway, whisking no longer dampened the animals’ response to painful stimuli. Now, Wang says, she and her team are eager to learn how this circuitry works with other parts of the brain to modulate the perception and response to painful stimuli.
Wang says the new findings might shed light on a condition called thalamic pain syndrome, a chronic pain disorder that can develop in patients after a stroke that affects the brain’s thalamus. “Such strokes may impair the functions of thalamic circuits that normally relay pure touch signals and dampen painful signals to the cortex,” she says.
Thalamic pain syndrome is an unfortunate outcome following a cerebrovascular accident (CVA). The pain experienced by the patient is centralized, neuropathic, and associated with temperature changes. Patients will often suffer from hyperalgesia and allodynia.
The prevalence of thalamic pain syndrome following a stroke is relatively high at up to eight percent of cases. Despite being common following a stroke, diagnosis is often difficult. The onset of a patient’s symptoms is often delayed following a CVA. A patient with a history of a CVA of the thalamus may not experience significant pain until months or years after their stroke.
Thalamic pain syndrome is now more commonly known as central post-stroke pain, while historically, it was known as Dejerine–Roussy syndrome. The nuances in these various terms are as follows. All cases of thalamic pain syndrome are a type of central post-stroke pain. However, not all cases of central post-stroke pain are thalamic in origin. A more accurate and broad definition of central post-stroke would be pain secondary to injury of the spinothalamic tract.
Thalamic pain syndrome is a term used interchangeably with centralized neuropathic pain. There is limited research complete for thalamic pain syndrome. There should be suspicion for thalamic pain syndrome in patients with a history of chronic and centralized pain and comorbid history of CVA.
Treatment options are limited and vary in efficacy. Alternative and integrative approaches to treatment are recommended to help improve pain and quality of life. Pharmacological options include neuropathic pain medications and opioid analgesics. More invasive treatment options include deep brain stimulation, surgery, and neuromodulation.
Given the complicated nature of thalamic pain syndrome, evaluation and treatment often require an interdisciplinary team that may consist of a neurologist, pain medicine specialist, or a neurosurgeon. Prognosis remains guarded. Providers must keep thalamic pain syndrome on their differential for all patients who have suffered a CVA and are complaining of symptoms of neuropathic pain.
Etiology
Thalamic pain syndrome most commonly occurs following a cerebrovascular accident. An isolated thalamic infarction is called a lacunar infarct. At the same time, a more expansive and extensive stroke typically derives its name after the more significant injured artery, such as a middle cerebral artery (MCA) infarction. However, a thalamic lesion or abscess can also cause sensory deficits, similar to thalamic pain syndrome. Thalamic pain syndrome can occur both following an ischemic stroke or hemorrhagic stroke.
The pain experienced in thalamic strokes is neuropathic.[1] Any injury to the thalamus can cause contralateral sensory deficits. Damage to the spinothalamic tract causes specific deficits in thermoregulation. The pain associated with thalamic pain syndrome can occur acutely following a stroke but also can occur in either the subacute period or years after the initial injury.[2]
The role of the thalamus is to act as a relay station for all sensory information within the brain except smell. Peripherally we are exposed to sensory information within our environment, and this information goes from our peripheral nervous system to our central nervous system (CNS). As the information reaches the CNS, it arrives in the thalamus. The thalamus acts as a way of decoding information and processing it. After it reaches the thalamus, it goes to the somatosensory cortex. Within the cortex, the information is interpreted. In the case of thalamic pain syndrome, this process becomes damaged.
Our sensory processing is lost, and we lose the ability to interpret tactile information accurately. Tactile information should not be painful at temperatures or at applied pressures that do not damage tissue. Pain should not be a symptom unless there is an acute injury. The afferent pathway from the thalamus to the cortex no longer functions correctly in central post-stroke pain.
The sensory information received by the thalamus is interpreted differently. Tactile stimuli become painful or painful stimuli are amplified and made worse.[3][4][5][6] When ordinary touch reproduces the pain, it is called allodynia, and when potentially painful stimuli are worse than expected, the patient is experiencing hyperalgesia.
Thalamic pain syndrome is a type of centralized pain. In centralized pain, the origin of the area of pain is stemming from the central nervous system. Central sensitization of pain occurs when the patient’s nervous system is persistently in a state of high activity. A persistently activated state decreases sensitivity to fire action potentials. An increase in firing of action potential leads to an amplification of neural signaling. Patients become hypersensitive to pain. This state of high alert is commonly known as the wind-up; clinically, it is known as temporal summation.
To make the diagnosis of thalamic pain syndrome, the patient’s pain is not attributable to a peripheral source. Any stroke along the spinothalamic tract can be suggestive of thalamic pain syndrome. Specifically, infarction of the ventral posterior nuclei of the thalamus is more likely to be associated with centralized post-stroke pain.[7]
There are a reduced number of opiate receptors within the thalamus, that may contribute to enhanced pain perception in cases of post-stroke pain, once the thalamus is damaged.[8][9][10] Hypersensitivity of the remaining nerves along the spinothalamic tract is a possible explanation of pain following infarction, secondary to microglial activation, leading to chronic activation.[11][12] Autonomic instability contributes to lower skin temperature in the areas of reported pain in patients with central post-stroke pain. Stress has also shown to worse pain.[13]
reference link : https://www.ncbi.nlm.nih.gov/books/NBK554490/
Original Research: Open access.
“Somatosensory cortical signature of facial nociception and vibrotactile touch–induced analgesia” by Fan Wang et al. Science Advances
