Neuroscience
-
Perineuronal net (PNN) is a specialized aggregate of the extracellular matrix, which is considered to be involved in regulation of structural plasticity of neuronal circuits. Here we examined the spatial and temporal differences in Wisteria floribunda agglutinin-labeled PNN intensity in single cells in the mouse hippocampus, where the neuronal circuits engaged in cognition and emotion are embedded in the dorsal and ventral parts, respectively. In young mice, the intensity of PNN was very low, and there were no significant dorsoventral differences in all hippocampal regions. ⋯ Contrary to expectations, developmental and aging-related changes in PV intensity were not comparable to those seen in PNN intensity. The correlation coefficients between PNN and PV intensities in single cells showed gradual decline during development and aging in the CA1 and CA3 regions, while there were little correlations in the dentate gyrus regardless of age. In summary, PNNs are differentially expressed in the dorsal and ventral hippocampal circuits during development and aging, indicating their possible role for cognition and emotion control.
-
The neurobiological mechanisms of spinal cord stimulation (SCS) when applied for neuropathic pain are still incompletely known. Previous research indicates that brainstem circuitry is pivotal for the SCS effect. The present study aims at exploring the possible contribution to the SCS effects of the pain controlling system emanating from the locus coeruleus (LC) in the brain stem. ⋯ No differences were found between these groups. In awake animals, lidocaine silencing of the ipsilateral LC or blocking of spinal noradrenergic system by intrathecal administration of α1,2 adrenoceptor antagonists failed to influence the antihypersensitivity effect of SCS. The present results indicate that the SCS-induced control of hypersensitivity in an experimental animal model of peripheral neuropathic pain may not be explained by the activation of direct spinal projections of noradrenergic LC neurons, while supraspinal projections of LC neurons still may play a role in the SCS effect.
-
In rodents as well as in many other mammalian and non-mammalian species, the arginine-vasopressin (AVP) system includes a parvocellular sexually dimorphic portion located within the bed nucleus of the stria terminalis (BST), the medial amygdaloid nucleus (MeA) and the lateral septum. In this system, males have more cells and denser projections than females, neurons show androgen and estrogen receptors, and gonadal hormones are required for the activation. However, the role of these hormones for the differentiation of the system is not clear. ⋯ To elucidate the role of androgens on differentiation and functioning of AVP parvocellular system, we compared male and female rats with a non-functional mutation of androgen receptor (Tfm, testicular feminization mutation) to their control littermates. Our data show that the lack of a functional androgen receptor significantly decreases the expression of AVP immunoreactivity within the BST and MeA of male Tfm. Thus supporting the hypothesis that androgens, through the action of their receptor, should have a relevant role in the organization and modulation of the AVP parvocellular sexually dimorphic system.
-
Although surgical trauma activates the anterior pituitary gland and elicits an increase in prolactin (PRL) serum levels that can modulate nociceptive responses, the role of PRL and the PRL-receptor (PRL-R) in thermal and mechanical hyperalgesia in postoperative pain is unknown. Acute postoperative pain condition was generated with the use of the hindpaw plantar incision model. Results showed endogenous PRL levels were significantly increased in serum, operated hindpaw and spinal cords of male and female rats 24h after incision. ⋯ Studies in KO mice showed no effect of PRL and PRL-R gene ablation on heat and cold hyperalgesia in male mice, while heat hyperlgesia were reduced 3-72 h post-surgery in female PRL and PRL-R KO mice. In contrast, PRL and PRL-R ablations significantly attenuated mechanical allodynia 3-72 h post-surgery in both male and female mice. Overall, we found elevated PRL levels in serum, hindpaws and spinal cords after incision, and identify a contributory role for the PRL system in postoperative pain responses to thermal stimuli in females and to mechanical stimuli in both males and females.
-
Cancer pain, particularly bone cancer pain, affects the quality of life of cancer patients, and current treatments are limited. Interleukin (IL)-33, a new member of the IL-1 super family, has been reported to be involved in the modulation of inflammatory pain. However, studies focused on its role in the modulation of cancer pain have been rare. ⋯ Meanwhile, concentrations of spinal IL-1β, IL-6 and TNF-a in the cancer-bearing ST2(-/-) mice had no significant changes. These data further suggested that IL-33/ST2 signaling played a vital role in cancer pain. Our results provided evidence that IL-33 and its receptor ST2 may be a potential therapeutic target for the treatment of pain in bone cancer patients.