Filling-In, Spatial Summation, and Radiation of Pain: Evidence for a Neural Population Code in the Nociceptive System – Free full-text PMC2804406 – J Neurophysiol. 2009 Dec
The receptive field organization of nociceptive neurons suggests that noxious information may be encoded by population-based mechanisms.
Electrophysiological evidence of population coding mechanisms has remained limited.
However, psychophysical studies examining interactions between multiple noxious stimuli can provide indirect evidence that neuron population recruitment can contribute to both spatial and intensity-related percepts of pain.
In the present study, pairs of thermal stimuli (35°C/49°C or 49°C/49°C) were delivered at different distances on the leg (0, 5, 10, 20, 40 cm) and abdomen (within and across dermatomes) and subjects evaluated pain intensity and perceived spatial attributes of stimuli.
Reports of perceived pain spreading to involve areas that were not stimulated (radiation of pain) were most frequent at 5- and 10-cm distances (χ2 = 34.107, P < 0.0001).
Perceived connectivity between two noxious stimuli (filling-in) was influenced by the distance between stimuli (χ2 = 16.756, P < 0.01), with the greatest connectivity reported at 5- and 10-cm separation distances.
Spatial summation of pain occurred over probe separation distances as large as 40 cm and six dermatomes (P < 0.05), but was maximal at 5- and 10-cm separation distances.
Taken together, all three of these phenomena suggest that interactions between recruited populations of neurons may support both spatial and intensity-related dimensions of the pain experience.
Population-based mechanisms of nociceptive processing in the CNS remain poorly understood due to lack of information about how large numbers of nociceptive neurons respond to incoming afferent information.
The present psychophysical data provide strong, yet indirect evidence that neuron recruitment contributes importantly to spatial dimensions of pain.
This recruitment of neurons can support interactions between multiple stimuli and can produce different perceptions such as radiation, spatial summation, and filling-in.
During clinical evaluation, the reported area of pain does not always reflect the origin of nociceptive information (de Leeuw et al. 1995a,b; Kreiner and Okeson 1999; Naranjo Hernandez et al. 1992).
The observed radiation of pain is consistent with the concept that intensely noxious stimuli recruit activity over a widely distributed population of neurons (Coghill et al. 1991). Sufficiently intense activation of neurons outside of the epicenter of the activated population may give rise to the perceptual experience that pain is spreading from the stimulated area (Fig. 7).
Filling-in is a phenomenon that allows the CNS to interpolate missing information to construct representations of continuous surfaces and demonstrates that physical stimuli presented do not necessary correspond to the final perception (Komatsu et al. 2002).
This phenomenon has been reported across visual, auditory, and somatosensory modalities
As with radiation of pain, the observed perception of filling-in is consistent with the concept that noxious stimuli recruit activity over a widely distributed population of neurons (Fig. 7).
Thus if two neuronal populations are activated by the two painful stimuli, such that there is an overlap of both populations, neurons in the overlapping region would be ideally positioned to contribute to the production of a final perception that there is connectivity between the two stimuli.
Spatial summation of pain
SSP is a classic example of integration between multiple noxious stimuli.
The present investigation found SSP over 40-cm distances between stimuli on the legand up to five to six dermatomes on the abdomen.
The present data indicate that SSP is modulated by the spatial distribution of the stimuli.
It was expected that the highest SSP would be seen when probes were closest together (i.e., 0 cm apart) and that SSP would decrease with increasing probe separation.
On the leg, however, pain intensity increased as probe separation increased from 0, to 5, to 10 cm and then decreased as separation of probes was increased to 20 and 40 cm (Fig. 4A)
SSP on the abdomen was also greater when stimuli were separated either vertically (across dermatomes) or horizontally (within dermatomes) than when they were placed side by side.
delivery of two noxious stimuli in relatively close proximity would be predicted to activate a neuronal population that would be generally similar to that activated by one stimulus alone.
This scenario is consistent with the relatively weak SSP seen at 0-cm separation distances. However, when stimuli are at an “optimal distance” from each other, each stimulus may activate somewhat different neuronal populations that overlap to some extent
The overlap of these populations may enable neurons that normally are not activated by either stimulus to reach threshold and contribute to the final output and/or may produce facilitated responses in neurons that were weakly activated by one stimulus alone
Consistent with this notion, spatial summation of pain was optimal at 5- to 10-cm separation distances.
These distances were also characterized by the most frequent reports of radiation and filling-in.
Individual differences in spatial tuning of nociceptive processing
1) the intensity of noxious stimuli influences the radiation of pain (Price et al. 1978),
2) higher noxious temperatures produce greater recruitment of neurons at the spinal level (Coghill et al. 1991), and
3) increasing noxious intensities evoke greater percepts of pain,
it is logical to postulate that increasing population recruitment [of neurons] would be associated with greater percepts of pain.
Accordingly, it follows that individuals who experience a great deal of pain from a stimulus of a given intensity could be expected to have greater population recruitment and thus greater radiation and SSP than that of individuals in whom the stimulus evoked a lesser experience of pain
Neither the frequency of radiation nor the magnitude of spatial summation was correlated with individual differences in pain sensitivity
Thus although studies of individual differences in pain have focused on intensity, individual differences in spatial tuning may represent an important and distinct dimension of the pain experience.