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Investigation of the Correlation between Postherpetic Itch and Neuropathic Pain over Time.

Postherpetic itch (PHI), or herpes zoster itch, is an intractable and poorly understood disease. We targeted 94 herpes zoster patients to investigate their pain and itch intensities at three separate stages of the condition (acute, subacute, and chronic). We used painDETECT questionnaire (PDQ) scores to investigate the correlation between PHI and neuropathic pain. Seventy-six patients were able to complete follow-up surveys. The prevalence of PHI was 47/76 (62%), 28/76 (37%), and 34/76 (45%) at the acute, subacute, and chronic stages, respectively. PHI manifestation times and patterns varied. We investigated the relationship of PHI with neuropathic pain using the visual analog scale (VAS), which is a measure of pain intensity, and the PDQ, which is a questionnaire used to evaluate the elements of neuropathic pain. The VAS and PDQ scores did not differ significantly between PHI-positive and PHI-negative patients. A large neuropathic component was not found for herpes zoster itch, suggesting that neuropathic pain treatments may not able to adequately control the itch. Accordingly, we suggest that a more PHI-focused therapy is required to address this condition.

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Attentional Engagement for Pain-Related Information among Individuals with Chronic Pain: The Role of Pain Catastrophizing.

Although the evidence of the attentional bias of chronic pain individuals toward pain-related information is established in the literature, few studies examined the time course of attention toward pain stimuli and the role of pain catastrophizing on attentional engagement toward pain-related information. This study examined the time course of attention to pain-related information and the role of pain catastrophizing on attentional engagement for pain-related information. Participants were fifty young adult participants with chronic pain (35% male, 65% female; M = 21.8 years) who completed self-report questionnaires assessing pain catastrophizing levels (Pain Catastrophizing Scale (PCS)), depression (the Center for Epidemiologic Studies Depression Scale (CES-D)), anxiety (State-Trait Anxiety Inventory (STAI)), and pain disability (the Pain Disability Index: (PDI)). Attentional engagements to pain- and anger-related information were measured by the eye tracker. Significant interaction effects were found between (1) time and stimulus type for pain-related information ( (5, 245) = 11.55, < 0.001) and (2) bias scores and pain catastrophizing ( (1, 48) = 6.736, < 0.05). These results indicated that the degree of increase for pain bias scores were significantly greater than anger bias scores as levels of pain catastrophizing increased. Results of the present study provided the evidence for the attentional bias and information processing model which has clinical implications; high levels of pain catastrophizing may impair individuals' ability to cope with chronic pain by increasing attentional engagement toward pain-related information. The present study can add knowledge to attentional bias and pain research as this study investigated the time course of attention and the role of pain catastrophizing on attentional engagement toward pain-related information for adults with chronic pain conditions.

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Fractalkine/CX3CR1 Contributes to Endometriosis-Induced Neuropathic Pain and Mechanical Hypersensitivity in Rats.

Pain is the most severe and common symptom of endometriosis. Its underlying pathogenetic mechanism is poorly understood. Nerve sensitization is a particular research challenge, due to the limitations of general endometriosis models and sampling nerve tissue from patients. The chemokine fractalkine (FKN) has been demonstrated to play a key role in various forms of neuropathic pain, while its role in endometriotic pain is unknown. Our study was designed to explore the function of FKN in the development and maintenance of peripheral hyperalgesia and central sensitization in endometriosis using a novel endometriosis animal model developed in our laboratory. After modeling, behavioral tests were carried out and the optimal time for molecular changes was obtained. We extracted ectopic tissues and L4-6 spinal cords to detect peripheral and central roles for FKN, respectively. To assess morphologic characteristics of endometriosis-like lesions-as well as expression and location of FKN/CX3CR1-we performed H&E staining, immunostaining, and western blotting analyses. Furthermore, inhibition of FKN expression in the spinal cord was achieved by intrathecal administration of an FKN-neutralizing antibody to demonstrate its function. Our results showed that implanted autologous uterine tissue around the sciatic nerve induced endometriosis-like lesions and produced mechanical hyperalgesia and allodynia. FKN was highly expressed on macrophages, whereas its receptor CX3CR1 was overexpressed in the myelin sheath of sciatic nerve fibers. Overexpressed FKN was also observed in neurons. CX3CR1/pp38-MAPK was upregulated in activated microglia in the spinal dorsal horn. Intrathecal administration of FKN-neutralizing antibody not only reversed the established mechanical hyperalgesia and allodynia, but also inhibited the expression of CX3CR1/pp38-MAPK in activated microglia, which was essential for the persistence of central sensitization. We concluded that the FKN/CX3CR1 signaling pathway might be one of the mechanisms of peripheral hyperalgesia in endometriosis, which requires further studies. Spinal FKN is important for the development and maintenance of central sensitization in endometriosis, and it may further serve as a novel therapeutic target to relieve persistent pain associated with endometriosis.

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Pain relief for outpatient hysteroscopy.

Hysteroscopy is increasingly performed in an outpatient setting. Pain is the primary reason for abandonment of procedure or incomplete assessment. There is no consensus upon routine use of analgesia during hysteroscopy.

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Low-level laser therapy for carpal tunnel syndrome.

The role of low-level laser therapy (LLLT) in the management of carpal tunnel syndrome (CTS) is controversial. While some trials have shown distinct advantages of LLLT over placebo and some other non-surgical treatments, other trials have not.

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Nociceptive Sensitization Reduces Predation Risk.

Sublethal injury triggers long-lasting sensitization of defensive responses in most species examined, suggesting the involvement of powerful evolutionary selection pressures [1]. In humans, this persistent nociceptive sensitization is often accompanied by heightened sensations of pain and anxiety [2]. While experimental [3] and clinical [4] evidence support the adaptive value of immediate nociception during injury, no direct evidence exists for adaptive benefits of long-lasting sensitization after injury. Recently, we showed that minor injury produces long-term sensitization of behavioral and neuronal responses in squid, Doryteuthis pealei [5, 6]. Here we tested the adaptive value of this sensitization during encounters between squid and a natural fish predator. Locomotion and other spontaneous behaviors of squid that received distal injury to a single arm (with or without transient anesthesia) showed no measurable impairment 6 hr after the injury. However, black sea bass given access to freely swimming squid oriented toward and pursued injured squid at greater distances than uninjured squid, regardless of previous anesthetic treatment. Once targeted, injured squid began defensive behavioral sequences [7, 8] earlier than uninjured squid. This effect was blocked by brief anesthetic treatment that prevented development of nociceptive sensitization [6, 9]. Importantly, the early anesthetic treatment also reduced the subsequent escape and survival of injured, but not uninjured, squid. Thus, while minor injury increases the risk of predatory attack, it also triggers a sensitized state that promotes enhanced responsiveness to threats, increasing the survival (Darwinian fitness) of injured animals during subsequent predatory encounters.

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Crystal structure of the µ-opioid receptor bound to a morphinan antagonist.

Opium is one of the world's oldest drugs, and its derivatives morphine and codeine are among the most used clinical drugs to relieve severe pain. These prototypical opioids produce analgesia as well as many undesirable side effects (sedation, apnoea and dependence) by binding to and activating the G-protein-coupled µ-opioid receptor (µ-OR) in the central nervous system. Here we describe the 2.8 Å crystal structure of the mouse µ-OR in complex with an irreversible morphinan antagonist. Compared to the buried binding pocket observed in most G-protein-coupled receptors published so far, the morphinan ligand binds deeply within a large solvent-exposed pocket. Of particular interest, the µ-OR crystallizes as a two-fold symmetrical dimer through a four-helix bundle motif formed by transmembrane segments 5 and 6. These high-resolution insights into opioid receptor structure will enable the application of structure-based approaches to develop better drugs for the management of pain and addiction.

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Comparison of Pain-Like behaviors in two surgical incision animal models in C57BL/6J mice.

Management of pain post-surgery is crucial for tissue healing in both veterinary and human medicine. Overuse of some analgesics such as opioids may lead to addictions and worsen pain syndromes (opioid-induced hyperalgesia), while underuse of it may affect the welfare of the patient. Therefore, the importance of using surgery models in laboratory animals is increasing, with the goal of improving our understanding of pain neurobiology and developing safer analgesics.

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Sex-related differences in experimental pain sensitivity in subjects with painful or painless neuropathy after surgical repair of traumatic nerve injuries.

Sex-related influences represent a contributor to greater pain sensitivity and have a higher prevalence of many chronic pain conditions, including neuropathic pain (NP), among women.

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Independent and combined associations of depressive symptoms and sleep disturbance with chronic pain in community-dwelling older adults.

There is limited evidence regarding whether depressive symptoms and sleep disturbance are independently or synergistically associated with chronic pain.

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