|Other Abstract||Chronic pain generally refers to pain lasting for more than three months. Acute pain makes us alert the surrounding harmful environment, but chronic pain cause cognitive impairment and bring great inconvenience to our daily life. Pre-attentive processing is the basis of our cognitive activities, which usually occurs before we process information, and is usually measured by mismatch negativity. Previous studies have found that chronic pain patients have impaired pre-attentive processing ability, but the results are not consistent, lack of systematic carding and animal experiments. In this study, we explored whether chronic pain affect the level of pre-attentive processing through meta-analysis and animal experiments.
In Study 1, we investigated the change of pre-attentive processing ability in patients with chronic pain by meta-analysis. We found 6 relevant literatures, which discussed the amplitude (5 literatures, 6 experiments) and latency (4 literatures, 5 experiments) of mismatch negativity respectively, involving 134 patients with chronic pain and 129 healthy controls. The results of meta-analysis showed that patients with chronic pain had impaired pre-attentive processing, including attenuation of amplitude and prolongation of latency of mismatch negativity. However, these results do not take into account that chronic pain patients are often mixed with different types of pain with different courses and taking different analgesics. We need to be verified by animal experiments.
In Study 2, we verified the existence of mismatch negativity in rodents through animal research, which can establishment rat model of pre-attentive processing. This experiment is the first time to use multi-feature paradigm to establishment the model of pre-attentive processing in animals. It was verified that there was mismatch negative in rats, and loudness deviation stimulation could induce more obvious amplitude, while gap stimulation could not induce MMN. This suggests that we should pay attention to the choice of sound stimulation properties in MMN research in the future, and choose the stimulation parameters suitable for rodents, rather than directly applying the sound stimulation in human pre-attentive processing research.
In Study 3, we first investigated the effects of different time after chronic pain on pre-attentive processing ability in rats. We investigate the changes of the processing level of pre-attentive processing in rats with chronic neuropathic pain and chronic inflammatory pain through two experiments. In the first experiment, we established chronic neuropathic pain model by spinal nerve ligation. In the second experiment, we established chronic inflammatory pain model by plantar injection of CFA. The results showed that the MMN latency of chronic neuropathic pain rats prolonged after 14 days of chronic pain model establishment, but no significant change in chronic inflammatory pain rats, which may be the reason for chronic inflammatory pain does not occupy much cognitive resources in the brain, so it can not affect the level of individual pre-attentive processing. This result also confirmed that chronic pain can cause pre-attentive procession function deficit, but only reflected in the model of chronic neuropathic pain.
In this study, we investigated the effects of chronic pain on pre-attentive processing step by step. It is found that chronic pain does affect the individual's pre-attentive processing ability, which is reflected in the prolongation of MMN latency in the late stage of chronic neuropathic pain. For the first time, we found that rodents are more sensitive to loudness stimuli by using the multi-feature paradigm to construct the pre-attentive processing model. All in all, this study laid an important foundation for further research on the effect of chronic pain on pre-attentive processing and exploring its neural mechanism, and provided a theoretical basis for exploring biomarkers of chronic pain that can be applied to clinical practice in the future.|