Why do hugs, hands, and caresses make us feel so comfortable?

iNature's pleasurable touches (eg, hugging, caressing, and patting) encode positive pleasure messages that promote emotional bonding, affinity behaviors, and well-being in social animals
.

Despite its profound implications, how pleasurable tactile information is encoded and transmitted from sensory neurons to the spinal cord remains unknown
.

On April 28, 2022, Zhoufeng Chen’s team at Washington University School of Medicine in St.
Louis (with Liu Benlong, Qiao Lina and Liu Kun as co-first authors) published a research paper titled “Molecular and neural basis of pleasant touch sensation” in Science Online.
The Human Pleasant Touch Conditioned Place Preference (PT-CPP) test shows that genetic ablation of spinal excitatory interneurons expressing prokineticin receptor 2 (PROKR2) or its ligand PROK2 in sensory neurons abolishes PT-CPP , without impairing pain and itching behavior in mice
.

The mutant mice showed severe impairments in stress responses and prosocial behaviors
.

PROKR2 neurons responded most strongly to gentle strokes and encoded reward values
.

Overall, the study identifies PROK2 as a long-sought neuropeptide that encodes and transmits pleasant touch to spinal PROKR2 neurons
.

These findings may have important implications for elucidating the mechanisms by which pleasurable touch deprivation leads to social avoidance behaviors and psychiatric disorders
.

Human touch consists of discriminative and emotional components
.

Discriminative touch detects the physical properties of tactile stimuli (eg, location, shape, texture, force, etc.
), while affective touch conveys emotional value mediated by social context
.

Pleasant touches, such as caressing and hugging, encode positive pleasure messages that promote emotional development, affinity behaviors, and well-being in social animals
.

Social contact is one of the most favored activities that may be evolutionarily conserved across the animal kingdom
.

In nonhuman primates, rodents, birds, and insects, mutual grooming (allogrooming) is important for strengthening and maintaining social bonds, reciprocity, attachment, and hierarchy
.

Severe social isolation increases social craving and reward-seeking behavior
.

Harlow's pioneering work showed that rhesus infants separated from their mothers have an innate desire to hug soft cloth for contact comfort and emotional needs, and that maternal touch is essential for the behavioral and psychological development of the offspring
.

Likewise, chronic lack of maternal care and positive social contact can have lasting negative effects on children's mental health
.

In fact, emotional tactile avoidance and deficits are some hallmarks of several neuropsychiatric disorders, including autism spectrum disorder (ASD)
.

Despite its profound implications, how pleasurable tactile information is encoded and transmitted from somatosensory neurons to the spinal cord remains unknown
.

The understanding of the molecular and neural circuits of pleasant touch is hindered by the lack of suitable animal models and methods that can accurately infer and assess the affective states of mice experiencing pleasant touch
.

Unlike discriminative touch, affective touch mediated by unmyelinated C fibers is a slow process
.

PROR2-PROKR2 mutant mice have severe impairments in stress responses and prosocial behaviors (figure from Science) hypothesized that pleasant touch is caused by slow-acting neuropeptides in C fibers and their cognate excitability in layer II of the spinal cord G protein-coupled receptors (GPCRs) encoded
.

In a search for lamina- and pattern-specific GPCRs, the study found that prokineticin receptor 2 (PROKR2) is uniquely expressed in lamina II of the spinal cord, and PROKR2 neurons represent a previously unknown population of spinal cord excitatory interneurons
.

Using an unbiased behavioral paradigm combining physiological tests, extracellular recordings, and genetic approaches, this study sought to examine the role of PROK2-PROKR2 signaling in pleasurable touch
.

Using the pleasurable tactile conditioned place preference (PT-CPP) test, this study shows that genetic ablation of spinal excitatory interneurons expressing prokineticin receptor 2 (PROKR2) or its ligand PROK2 in sensory neurons can Eliminate PT-CPP without impairing pain and itching behavior in mice
.

The mutant mice showed severe impairments in stress responses and prosocial behaviors
.

PROKR2 neurons responded most strongly to gentle strokes and encoded reward values
.

Overall, the study identifies PROK2 as a long-sought neuropeptide that encodes and transmits pleasant touch to spinal PROKR2 neurons
.

These findings may have important implications for elucidating the mechanisms by which pleasurable touch deprivation leads to social avoidance behaviors and psychiatric disorders
.

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