Spirocyclic sulfonamides with carbonic anhydrase inhibitory and anti-neuropathic pain activity

A novel series of 4-oxo-spirochromane bearing primary sulfonamide group were synthetized as Carbonic Anhydrase inhibitors (CAIs) and tested for their management of neuropathic pain. Indeed, CAs have been recently validated as novel therapeutic targets in neuropathic pain. All compounds, here reported, showed strong activity against hCA II and hCA VII with K_I values in the low or sub-nanomolar range. Two compounds (6d and 6l) showed good neuropathic pain attenuating effects and longer duration than drug reference acetazolamide in an animal model of oxaliplatin induced neuropathy.     

Does Anthropomorphism of Dogs Affect Pain Perception in Animal-Assisted Interventions? An Exploratory Study

The purpose of this exploratory study was to determine the effects of anthropomorphism of a therapy dog on pain perception during an animal-assisted intervention. Participants were 32 college women who were randomly assigned to the anthropomorphism condition or the control condition. All participants engaged in a pretest cold pressor task to measure base-line individual differences in pain tolerance and perceptions of pain intensity and pain unpleasantness. After completing this task, participants in the anthropomorphism group engaged in a task intended to prime them to view a therapy dog anthropomorphically. Specifically, they rated photos of dogs on a series of humanlike traits (e.g., “this dog would be a good listener”). Participants in the control condition rated photos of dogs on a series of canine traits (e.g., “this dog would make a good watchdog”). After this experimental manipulation, participants engaged in a second cold pressor task in the presence of a therapy dog and the therapy dog handler. We hypothesized that participants in the anthropomorphism group would demonstrate greater pain tolerance and report lower levels of pain intensity and pain unpleasantness during the second cold pressor task than participants in the control group. Results provide partial support for these hypotheses. Participants in the anthropomorphism group reported lower posttest pain intensity than participants in the control group. In addition, they demonstrated greater posttest pain tolerance than participants in the control group—but only under conditions of medium or high pretest pain tolerance. The two groups did not differ with respect to posttest pain unpleasantness. The results of this exploratory study provide preliminary evidence that prompting individuals to view a therapy dog anthropomorphically may augment their experience of pain relief from a therapy dog visit.     

Effect of laterality discrimination on joint position sense and cervical range of motion in patients with chronic neck pain: a randomized single-blind clinical trial

Purpose: The main objective of the present study was to evaluate the effects of laterality discrimination training on neck joint position sense and cervical range of motion (ROM) in patients with chronic non-specific neck pain (NSCNP).

Materials and methods: Forty-eight patients with NSCNP were randomly assigned to the neck group (NG) that observed neck images or the foot group (FG) that observed foot images. Response time, response accuracy, cervical ROM, and joint position error (JPE) were the main variables. The secondary outcome measures included psychosocial variables.

Results: Differences between groups in the cervical ROM for flexion (p?=?.043) were obtained, being NG group the one which obtained greater values. NG showed an improvement in right rotation (p?=?.018) and a decrease in flexion was found in the FG (p?=?.039). In JPE, differences between groups were obtained in the left rotation (p?=?.021) and significant changes were found in the NG for flexion, extension, and left rotation movements (p?<?.05). Moderate associations were found between left and right accuracy regarding to post-intervention flexion and right rotation (r?=?0.46, r?=?0.41; p?<?.05) in NG.

Conclusion: Improvements in cervical range of motion and joint position sense are obtained after the performance of the laterality discrimination task of images of the neck but not the feet. Visualization of images of the painful region presents moderate correlations with the accuracy and response time in the movements of flexion and right rotation.     

MiR-134-5p attenuates neuropathic pain progression through targeting Twist1

Neuropathic pain is a kind of chronic pain because of dysfunctions of somatosensory nerve system. Recently, many studies have demonstrated that microRNAs (miRs) play crucial roles in neuropathic pain development. This study was designed to investigate the effects of miR-134-5p on the process of neuropathic pain progression in a rat model established by chronic sciatic nerve injury (CCI). First, we observed that miR-134-5p was significantly decreased in CCI rat models. Overexpression of miR-134-5p strongly alleviated neuropathic pain behaviors including mechanical and thermal hyperalgesia. Meanwhile, inflammatory cytokine expression, such as IL-6, IL-1β and TNF-α in CCI rats were greatly repressed by upregulation of miR-134-5p. Twist1 has been widely regarded as a poor prognosis biomarker in diverse diseases. Here, by using bioinformatic analysis, 3′-untranslated region (UTR) of Twist1 was predicted to be a downstream target of miR-134-5p in our study. Here, we found that overexpression of miR-134-5p was able to suppress Twist1 dramatically. Furthermore, it was exhibited that Twist1 was increased in CCI rats time-dependently and Twist1 was inhibited in vivo. Subsequently, downregulation of Twist1 in CCI rats could depress neuropathic pain progression via inhibiting neuroinflammation. In conclusion, our current study indicated that miR-134-5p may inhibit neuropathic pain development through targeting Twist1. Our findings suggested that miR-134-5p might provide a novel therapeutic target for neuropathic pain.     

What really is the nature of suffering? Three problems with Eric Cassell’s concept of distress

Eric Cassell famously defined suffering as a person’s severe distress at a threat to their personal integrity. This article draws attention to some problems with the concept of distress in this theory. In particular, I argue that Cassell’s theory turns on distress but does not define it, which, in light of the complexity of distress, problematizes suffering in three ways: first, suffering becomes too equivocal to apply in at least some cases that Cassell nevertheless identifies as suffering; second, Cassell’s account does not explain what sort of experience suffering is, resulting in theoretical and practical difficulties in distinguishing it from other medical conditions; third, there is good reason to believe that, in medical contexts, ‘distress’ just means ‘suffering’ or some cognate concept not yet distinguished from it, rendering Cassell’s theory circular. I consider a rebuttal to my objections and reply, concluding that Cassell’s theory of suffering needs a definition of distress to settle what the nature of suffering really is.     

猫皮层体感Ⅱ区内脏伤害感受神经元的电生理特性及形态特征

应用胞内记录和标记技术,观察了猫皮质第Ⅱ感觉区内脏大神经代表区的神经元对电刺激内脏大神经反应诱发反应及形态特征。结果表明,在２５１个记录单位中,有１０９个为内脏伤害性感受神经元,其诱发反应分为兴奋性、抑制性及混合性三类。在形式上ＩＳＰＳ及ＥＰＳＰ－ＩＰＳＰ序列反应较多。对其中２１个神经元用神经生物素进行细胞内电泳标记,显示细胞的形态特点是胞体较小,分布于皮质Ⅱ、Ⅲ、Ⅴ层,其中兴奋性和神经元形态多为