A roadmap to solve outstanding questions and challenges
Using more standardized pupillometric setups, such as the one introduced
in this study, opens up exciting possibilities. Pupil responses to touch
can be used to investigate at which level tactile stimulation is
processed. For instance, if tactile stimuli elicit a pupil response
without explicit conscious perception, it implies that the stimulus is
only implicitly processed, a dissociation that resembles a condition
termed numbsense (Gallace & Spence, 2008; Rossetti et al., 1995). To
gain further insight into the patterns of pupil response for consciously
and unconsciously perceived stimuli, measuring pupil responses after
tactile stimulation on numbed skin using local anesthesia could be
employed. While it has been shown that pupil responses scale with the
intensity of nociceptive stimuli (Chapman et al., 1999; Sabourdin et
al., 2018; Wildemeersch et al., 2018) and with the concentration of
administered analgesia (Aissou et al., 2012; Larson et al., 1997), there
is a gap in understanding pupil response after non-noxious tactile
stimulation on a body location under local anesthesia. Alternatively,
paradigms could be used in which the stimuli are presented at the
threshold of detection (Gusso et al., 2022) or in which attention for
the stimulated location is manipulated. The resulting findings could
contribute to a better understanding of (subtypes of) tactile hypo- and
hypersensitivity in pathologies such as chronic pain (fibromyalgia,
complex regional pain syndrome) and autism spectrum disorder, and
neuropsychological disorders such as tactile neglect and extinction
following brain damage. Potentially, characteristics of the pupil
response following tactile stimulation may be used to index the level of
(residual) processing of touch, and consequently predict recovery or
outcomes of rehabilitation therapy.
The differences observed in pupil responses across the three stimulated
body locations in our study were in line with the known patterns of
subjective tactile sensitivity (Weinstein, 1968). The pupillometric
index could be used to expand these findings and create a “pupil-based
homunculus” – where pupil responses serve as a detailed map, mirroring
the processing intensity of tactile sensation in the brain. This could
potentially lead to novel insights on the underlying neural mechanisms
of differences in tactile sensitivity of different body parts. Whilst
our results show clear evidence of stronger pupil dilation to
stimulation to more subjectively sensitive body parts and stronger
stimulation, at this point, we cannot elucidate which mechanical
receptor types drove these effects the strongest. However, the
systematic variation of stimulation frequency at constant amplitude
might allow to narrow down this question, as different types of
mechanoreceptors have different frequency ranges to which they are most
sensitive (Delhaye et al., 2018). For instance, Meissner’s Corpuscles
reportedly respond strongest to stimulation in the band of 10 to 50 Hz
(Piccinin, MA, Miao, JH, Schwartz, 2022), whilst Pacinian Corpuscles
should respond stronger to stimulation at much higher frequencies such
as 250 Hz (Talbot et al., 1968). A straightforward prediction is
therefore that matching stimulation intensities trigger certain receptor
types specifically. Comparing pupil responses to these different
frequencies at constant amplitude could therefore allow to make
inferences about relative receptor distributions/proportions.
While the current method effectively shows the predicted differences
between conditions at a group level, substantial individual variability
poses a challenge. To enhance the method for both research and clinical
use, it is crucial to optimize the signal-to-noise ratio, and obtain a
measure that ideally encompasses a low number of trials and is still
reliable.