Abstract
Chronic inflammatory pain can induce emotional diseases. Electroacupuncture (EA) has effects on chronic pain and pain-related anxiety. Protein kinase Mzeta (PKMzeta) has been proposed to be essential for the maintenance of pain and may interact with GluR1 to maintain CNS plasticity in the anterior cingulate cortex (ACC). We hypothesized that the PKMzeta-GluR1 pathway in the ACC may be involved in anxiety-like behaviors of chronic inflammatory pain and that the mechanism of EA regulation of pain emotion may involve the PKMzeta pathway in the ACC. Our results showed that chronic inflammatory pain model decreased the paw withdrawal threshold (PWT) and increased anxiety-like behaviors. The protein expression of PKCzeta, p-PKCzeta (T560), PKMzeta, p-PKMzeta (T560), and GluR1 in the ACC of the model group were remarkably enhanced. EA increased PWT and alleviated anxiety-like behaviors. EA significantly inhibited the protein expression of p-PKMzeta (T560) in the ACC, and only a downward trend effect for other substances. Further, the microinjection of ZIP remarkably reversed PWT and anxiety-like behaviors. The present study provides direct evidence that the PKCzeta/PKMzeta-GluR1 pathway is related to pain and pain-induced anxiety-like behaviors. EA treatment both increases pain-related somatosensory behavior and decreases pain-induced anxiety-like behaviors by suppressing PKMzeta activity in the ACC.
Highlights
Pain has both sensory-discriminative and emotionalaffective dimensions
Chronic inflammatory pain induced by the injection of complete Freund’s adjuvant (CFA) was found to reduce the paw withdrawal threshold (PWT) and to increase anxiety-like behaviors
EA significantly inhibited the expression of p-Protein kinase Mzeta (PKMzeta) (T560) protein in the anterior cingulate cortex (ACC) of CFA-injected rats and showed a trend to reduce the expression of PKCzeta, p-PKCzeta (T560), PKMzeta, and GluR1 protein
Summary
It has been known that a large proportion of chronic pain patients have accompanying sleep, depressive, and/or anxiety disorders that contribute to a deterioration in the quality of life [1, 2]. Patients with chronic pain are up to 2-3 times more likely to develop anxiety disorders [3, 4]. Chronic inflammatory pain, which is one of the most common chronic pain conditions, is strongly associated with psychiatric disorders (e.g., anxiety and depressive disorders) [5]. Previous studies by our lab and others have shown that inducing chronic inflammatory pain for four weeks using complete Freund’s adjuvant (CFA) results in the development of anxiety-like behaviors [6,7,8]
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