Biology subjects

Liljencrantz, J.

Publications and source records attributed to Liljencrantz, J..

3 recordsLinked to original sources

bioRxiv2023

PIEZO2-dependent rapid pain system in humans and mice.

The PIEZO2 ion channel is critical for transducing light touch into neural signals but is not considered necessary for transducing acute pain in humans. Here, we discovered an exception - a form of mechanical pain evoked by hair pulling. Based on observations in a rare group of individuals with PIEZO2 deficiency syndrome, we demonstrated that hair-pull pain is dependent on PIEZO2 transduction. Studies in control participants showed that hair-pull pain triggered a distinct nocifensive response, including a nociceptive reflex. Observations in rare A{beta} deafferented individuals and nerve conduction block studies in control participants revealed that hair-pull pain perception is dependent on A{beta} input. Single-unit axonal recordings revealed that a class of cooling-responsive myelinated nociceptors in human skin is selectively tuned to painful hair-pull stimuli. Further, we pharmacologically mapped these nociceptors to a specific transcriptomic class. Finally, using functional imaging in mice, we demonstrated that in a homologous nociceptor, Piezo2 is necessary for high-sensitivity, robust activation by hair-pull stimuli. Together, we have demonstrated that hair-pulling evokes a distinct type of pain with conserved behavioral, neural, and molecular features across humans and mice.

neuroscience↗

bioRxiv2023

The role of cutaneous Aβ fibers in human nocifensive functions: Nerve block study on painful withdrawal reflex responses

The nociceptive withdrawal reflex (NWR) is a protective limb withdrawal response triggered by painful stimuli, used to assess spinal nociceptive excitability. Conventionally, the NWR is understood as having two reflex responses: a short-latency A{beta}-mediated response, considered tactile, and a longer-latency A{delta}-mediated response, considered nociceptive. However, nociceptors with conduction velocities similar to A{beta} tactile afferents have been identified in human skin. In this study, we investigated the effect of a preferential conduction block of A{beta} fibers on pain perception and NWR signaling evoked by intradermal electrical stimulation in healthy participants. We recorded a total of 198 NWR responses in the intact condition, and no dual reflex responses occurred within our latency bandwidth (50-150 ms). The current intensity required to evoke the NWR was magnitude higher than the perceptual pain threshold, indicating that NWR did not occur before pain was felt. In the block condition, when the A{beta}-mediated tuning fork sensation was lost while A{delta}-mediated nonpainful cooling was still detectable (albeit reduced), we observed that the reflex was abolished. Further, short-latency electrical pain intensity at pre-block thresholds was greatly reduced, with any residual pain sensation having a longer latency. Although electrical pain was unaffected at suprathreshold current intensities, the reflex could not be evoked despite a two-fold increase in the pre-block current intensity and a five-fold increase in the pre-block pulse duration. These observations lend support to the possible involvement of A{beta}-fiber inputs in pain and reflex signaling.

neuroscience↗

bioRxiv2022

Aβ-CT affective touch: Touch pleasantness ratings for gentle stroking and deep pressure exhibit dependence on A-fibers

Gentle stroking of the skin is a common social touch behavior with positive affective consequences. A preference for slow versus fast stroking of hairy skin has been closely linked to the firing of unmyelinated C-tactile (CT) somatosensory afferents. Because the firing of CT afferents strongly correlates with touch pleasantness, the CT pathway has been considered a social-affective sensory pathway. Recently, ablation of the spinothalamic pathway-thought to convey all C-fiber sensations-in patients with cancer pain impaired pain, temperature, and itch, but not ratings of pleasant touch. This suggested integration of A and CT fiber input in the spinal cord, or A-fiber contributions to computations of touch pleasantness in the brain. However, the causal contribution of A-fibers to touch pleasantness- in humans without pain-remains unknown. In the current, single-blinded study we performed two types of peripheral nerve blocks in healthy adults to temporarily eliminate the contribution of A-fibers to touch perception. Our findings show that when A-fiber function is greatly diminished, the perceived intensity and pleasantness of both gentle stroking and deep pressure are nearly abolished. These findings demonstrate that explicit perception of the pleasantness of CT-targeted brushing and pressure both critically depend on A-fibers.

neuroscience↗