OBJECTIVES: This study aimed to investigate whether the microglia in the spinal trigeminal nucleus caudal part (Sp5C) were activated in a rat model of trigeminal neuralgia and to explore whether the activation level of microglia is consistent with maxillofacial pain level. METHODS: Chronic constriction injury of trigeminal nerve (CCI) was induced by partial ligation of infraorbital nerve (IoN) in rats. The behavioral change of rats observed at D1, D5, D10, D15, and D30 days post-surgery and the change of pain threshold were detected with electronic Von Frey filaments served as an evaluation index of maxillofacial pain. Weight change was measured by weighing. Ionized calcium binding adaptor molecule-1 (Iba-1) expression level of Sp5C at each time point was detected, and three microglia morphological categories were analyzed by immunohistochemical staining. RESULTS: The changes of behavioral and pain threshold suggested the maxillofacial pain level first increased and then decreased post-surgery in the IoN-CCI group. Both the expressions of Iba-1 and proportion of ameboid morphology in ipsilateral Sp5C increased from D1 and reached their peaks in D10 and D5, respectively. Then, they recovered nearly to the same level with contralateral Sp5C on D30. This trend was consistent with the maxillofacial change. CONCLUSIONS The model of trigeminal neuralgia in rats constructed by partial ligation of infraorbital nerve can induce the activation of microglia in Sp5C, and the activation level is consistent with maxillofacial pain, which reached its peak at around D10 post-surgery.
Rats ; Animals ; Trigeminal Neuralgia ; Rats, Sprague-Dawley ; Microglia ; Pain Threshold/physiology* ; Pain

Low-level laser therapy (LLLT) may have an effect on the pain associated with orthodontic treatment. The aim of this study was to evaluate the effect of LLLT on pain and somatosensory sensitization induced by orthodontic treatment. Forty individuals (12-33 years old; mean ± standard deviations: 20.8 ± 5.9 years) scheduled to receive orthodontic treatment were randomly divided into a laser group (LG) or a placebo group (PG) (1:1). The LG received LLLT (810-nm gallium-aluminium-arsenic diode laser in continuous mode with the power set at 400 mW, 2 J·cm) at 0 h, 2 h, 24 h, 4 d, and 7 d after treatment, and the PG received inactive treatment at the same time points. In both groups, the non-treated side served as a control. A numerical rating scale (NRS) of pain, pressure pain thresholds (PPTs), cold detection thresholds (CDTs), warmth detection thresholds (WDTs), cold pain thresholds (CPTs), and heat pain thresholds (HPTs) were tested on both sides at the gingiva and canine tooth and on the hand. The data were analysed by a repeated measures analysis of variance (ANOVA). The NRS pain scores were significantly lower in the LG group (P = 0.01). The CDTs, CPTs, WDTs, HPTs, and PPTs at the gingiva and the PPTs at the canine tooth were significantly less sensitive on the treatment side of the LG compared with that of the PG (P < 0.033). The parameters tested also showed significantly less sensitivity on the non-treatment side of the LG compared to that of the PG (P < 0.043). There were no differences between the groups for any quantitative sensory testing (QST) measures of the hand. The application of LLLT appears to reduce the pain and sensitivity of the tooth and gingiva associated with orthodontic treatment and may have contralateral effects within the trigeminal system but no generalized QST effects. Thus, the present study indicated a significant analgesia effect of LLLT application during orthodontic treatment. Further clinical applications are suggested.
Adolescent ; Adult ; Female ; Humans ; Low-Level Light Therapy ; methods ; Male ; Pain Management ; Pain Measurement ; Pain Threshold ; physiology ; Tooth Movement Techniques ; adverse effects ; Toothache ; etiology ; radiotherapy ; Treatment Outcome ; Young Adult

Cognition and pain share common neural substrates and interact reciprocally: chronic pain compromises cognitive performance, whereas cognitive processes modulate pain perception. In the present study, we established a non-drug-dependent rat model of context-based analgesia, where two different contexts (dark and bright) were matched with a high (52°C) or low (48°C) temperature in the hot-plate test during training. Before and after training, we set the temperature to the high level in both contexts. Rats showed longer paw licking latencies in trials with the context originally matched to a low temperature than those to a high temperature, indicating successful establishment of a context-based analgesic effect in rats. This effect was blocked by intraperitoneal injection of naloxone (an opioid receptor antagonist) before the probe. The context-based analgesic effect also disappeared after optogenetic activation or inhibition of the bilateral infralimbic or prelimbic sub-region of the prefrontal cortex. In brief, we established a context-based, non-drug dependent, placebo-like analgesia model in the rat. This model provides a new and useful tool for investigating the cognitive modulation of pain.
Action Potentials ; drug effects ; physiology ; Analgesics ; pharmacology ; therapeutic use ; Animals ; Disease Models, Animal ; Electric Stimulation ; Female ; In Vitro Techniques ; Naloxone ; pharmacology ; Narcotic Antagonists ; pharmacology ; Optogenetics ; Pain ; drug therapy ; pathology ; physiopathology ; Pain Measurement ; drug effects ; Pain Threshold ; drug effects ; physiology ; Patch-Clamp Techniques ; Physical Stimulation ; Prefrontal Cortex ; drug effects ; metabolism ; pathology ; Pyramidal Cells ; drug effects ; physiology ; Rats ; Rats, Sprague-Dawley ; Time Factors

Accumulating evidence suggests that obesity is associated with chronic pain. However, whether obesity is associated with acute inflammatory pain is unknown. Using a well-established obese mouse model induced by a high-fat diet, we found that: (1) the acute thermal pain sensory threshold did not change in obese mice; (2) the model obese mice had fewer nociceptive responses in formalin-induced inflammatory pain tests; restoring the obese mice to a chow diet for three weeks partly recovered their pain sensation; (3) leptin injection induced significant phosphorylation of STAT3 in control mice but not in obese mice, indicating the dysmodulation of topical leptin-leptin receptor signaling in these mice; and (4) leptin-leptin receptor signaling-deficient mice (ob/ob and db/db) or leptin-leptin receptor pathway blockade with a leptin receptor antagonist and the JAK2 inhibitor AG 490 in wild-type mice reduced their nociceptive responses in formalin tests. These results indicate that leptin plays a role in nociception induced by acute inflammation and that interference in the leptin-leptin receptor pathway could be a peripheral target against acute inflammatory pain.
Animals ; Diet, High-Fat ; adverse effects ; Inflammation ; chemically induced ; metabolism ; Leptin ; metabolism ; pharmacology ; Male ; Mice ; Mice, Inbred C57BL ; Nociception ; drug effects ; physiology ; Nociceptive Pain ; etiology ; metabolism ; Obesity ; complications ; metabolism ; Pain Measurement ; Pain Threshold ; drug effects ; physiology ; Receptors, Leptin ; metabolism ; Signal Transduction ; drug effects ; physiology

Tetanic stimulation of the sciatic nerve (TSS) triggers long-term potentiation in the dorsal horn of the spinal cord and long-lasting pain hypersensitivity. CX3CL1-CX3CR1 signaling is an important pathway in neuronal-microglial activation. Nuclear factor κB (NF-κB) is a key signal transduction molecule that regulates neuroinflammation and neuropathic pain. Here, we set out to determine whether and how NF-κB and CX3CR1 are involved in the mechanism underlying the pathological changes induced by TSS. After unilateral TSS, significant bilateral mechanical allodynia was induced, as assessed by the von Frey test. The expression of phosphorylated NF-κB (pNF-κB) and CX3CR1 was significantly up-regulated in the bilateral dorsal horn. Immunofluorescence staining demonstrated that pNF-κB and NeuN co-existed, implying that the NF-κB pathway is predominantly activated in neurons following TSS. Administration of either the NF-κB inhibitor ammonium pyrrolidine dithiocarbamate or a CX3CR1-neutralizing antibody blocked the development and maintenance of neuropathic pain. In addition, blockade of NF-κB down-regulated the expression of CX3CL1-CX3CR1 signaling, and conversely the CX3CR1-neutralizing antibody also down-regulated pNF-κB. These findings suggest an involvement of NF-κB and the CX3CR1 signaling network in the development and maintenance of TSS-induced mechanical allodynia. Our work suggests the potential clinical application of NF-κB inhibitors or CX3CR1-neutralizing antibodies in treating pathological pain.
Animals ; Antibodies ; therapeutic use ; Antioxidants ; therapeutic use ; CX3C Chemokine Receptor 1 ; immunology ; metabolism ; Cytokines ; metabolism ; Disease Models, Animal ; Enzyme Inhibitors ; therapeutic use ; Ganglia, Spinal ; drug effects ; metabolism ; Hyperalgesia ; etiology ; metabolism ; Nerve Tissue Proteins ; metabolism ; Pain Threshold ; physiology ; Physical Stimulation ; adverse effects ; Proline ; analogs & derivatives ; therapeutic use ; Rats ; Rats, Sprague-Dawley ; Sciatic Nerve ; physiology ; Signal Transduction ; physiology ; Spinal Cord ; drug effects ; metabolism ; Thiocarbamates ; therapeutic use ; Up-Regulation ; drug effects ; physiology

Empathy, a basic prosocial behavior, is referred to as an ability to understand and share others' emotional state. Generally, empathy is also a social-behavioral basis of altruism. In contrast, impairment of empathy development may be associated with autism, narcissism, alexithymia, personality disorder, schizophrenia and depression. Thus, study of the brain mechanisms of empathy has great importance to not only scientific and clinical advances but also social harmony. However, research on empathy has long been avoided due to the fact that it has been considered as a distinct feature of human beings from animals, leading to paucity of knowledge in the field. In 2006, a Canadian group from McGill University found that a mouse in pain could be shared by its paired cagemate, but not a paired stranger, showing decreased pain threshold and increased pain responses through emotional contagion while they were socially interacting. In 2014, we further found that a rat in pain could also be shared by its paired cagemate 30 min after social interaction, showing long-term decreased pain threshold and increased pain responses, suggesting persistence of empathy for pain (empathic memory). We also mapped out that the medial prefrontal cortex, including the anterior cingulate cortex, prelimbic cortex and infralimbic cortex, is involved in empathy for pain in rats, suggesting that a neural network may be associated with development of pain empathy in the CNS. In the present brief review, we give a brief outline of the advances and challenges in study of empathy for pain in humans and animals, and try to provide a novel bio-psychosocial-behavioral model for study of pain and its emotional comorbidity using laboratory animals.
Animals ; Cerebral Cortex ; physiology ; Emotions ; Empathy ; Gyrus Cinguli ; physiology ; Humans ; Mice ; Models, Animal ; Pain ; Pain Threshold ; Prefrontal Cortex ; physiology ; Rats

BACKGROUND/AIMS: DA-9701 is a newly developed drug made from the vegetal extracts of Pharbitidis semen and Corydalis tuber. The aim of this study was to evaluate the effect of DA-9701 on colorectal distension (CRD)-induced visceral hypersensitivity in a rat model. METHODS: Male Sprague-Dawley rats were subjected to neonatal colon irritation (CI) using CRD at 1 week after birth (CI group). At 6 weeks after birth, CRD was applied to these rats with a pressure of 20 to 90 mm Hg, and changes in the mean arterial pressure (MAP) were measured at baseline (i.e., without any drug administration) and after the administration of different doses of DA-9701. RESULTS: In the absence of DA-9701, the MAP changes after CRD were significantly higher in the CI group than in the control group at all applied pressures. In the control group, MAP changes after CRD were not significantly affected by the administration of DA-9701. In the CI group, however, the administration of DA-9701 resulted in a significant decrease in MAP changes after CRD. The administration of DA-9701 at a dose of 1.0 mg/kg produced a more significant decrease in MAP changes than the 0.3 mg/kg dose. CONCLUSIONS: The administration of DA-9701 resulted in a significant increase in pain threshold in rats with CRD-induced visceral hypersensitivity.
Analgesics/administration & dosage/*pharmacology ; Animals ; Arterial Pressure/drug effects ; Colon, Descending/physiology ; Dilatation/methods ; Gastrointestinal Agents/administration & dosage/*pharmacology ; Male ; Pain Threshold/drug effects ; Plant Preparations/administration & dosage/*pharmacology ; Rats, Sprague-Dawley ; Visceral Pain/physiopathology/*prevention & control

OBJECTIVETo observe the changes of the mechanical pain threshold in the rat model of autoimmune prostatitis, explore the mechanism of autoimmune prostatitis pain and offer some animal experimental evidence for the drug therapy of the condition.

METHODSTwenty male Wistar rats weighing 180 - 220 g were divided into a model and a control group. The autoimmune prostatitis model was established by subcutaneous injection of an extract of male rat prostate glands (RPG) at 60 mg/ml in Freund's complete adjuvant (FCA) and pertussis-diphtheria-tetanus vaccine at 0 and 30 days, respectively. Mechanical tactile hyperalgesia was measured once a week using Von Frey Filaments from the beginning of the study. At 8 weeks after modeling, the rats were sacrificed and the prostate tissues harvested for observation of histomorphological changes by HE staining.

RESULTSHE staining revealed different degrees of benign prostatitis in the model rats. Compared with the controls, the mechanical pain threshold in the model rats was significantly decreased with the increased time of modeling, from (65.52 +/- 6.27) g at 0 week to (23.67 +/- 4.09) g at 8 weeks (P < 0.01). Statistically significant differences were found in the variation trend at different time points between the two groups (P < 0.01).

CONCLUSIONAutoimmune prostatitis models were successfully established in rats and hyperalgesia was induced after modeling.

Animals ; Autoimmune Diseases ; physiopathology ; Disease Models, Animal ; Male ; Pain Threshold ; physiology ; Prostatitis ; immunology ; physiopathology ; Rats ; Rats, Wistar

OBJECTIVE: To explore the application of quantitative temperature testing (QTT) in forensic identification and clinical diagnosis of neurogenic erectile dysfunction (NED). METHODS: TSA-II-NeuroSensory Analyzer was used to measure the thresholds of four kinds of sensory, including cold, cold pain, heat, heat pain, in 22 normal and 35 NED patients at dorsal glans (DG), left thigh interior (LTI) and left thenar (LT). To calculate the relative thresholds of the sensory mentioned above between DG and LTI (DG/LTI), and between DG and LT (DG/LT). Then to analyze those thresholds and the relative thresholds. RESULTS: NED group showed significant higher threshold than the normal group in DG-heat, DG-heat pain, LTI-heat, LTI-heat pain, DG/LTI-heat, DG/LT-heat, DG/LT-heat pain (P < 0.05). CONCLUSION The threshold of QTT at dorsal glans could be used as an accessory indicator in forensic medicine and clinical diagnosis of NED.
Adult ; Case-Control Studies ; Erectile Dysfunction/physiopathology* ; Hand/physiology* ; Humans ; Male ; Nervous System Diseases/physiopathology* ; Neurologic Examination/methods* ; Pain Threshold ; Penis/physiopathology* ; Sensory Thresholds ; Temperature ; Thermosensing

Trigeminal neuralgia is a paroxysmal disorder with severely disabling facial pain and thus continues to be a real therapeutic challenge. At present there are few effective drugs for treatment of this pain. The present study was aimed to explore the involvement of BK(Ca) channels and Kv channels in the mechanical allodynia in a rat model of trigeminal neuropathic pain. Here the effectiveness of drug target injection at the trigeminal ganglion through the infraorbital foramen was first evaluated by immunofluorescence and animal behavior test. Trigeminal neuropathic pain model was established by chronic constriction injury of the infraorbital nerve (ION-CCI) in rats. BK(Ca) channel agonist and Kv channel antagonist were administered into the trigeminal ganglion in ION-CCI rats and sham rats by the above target injection method, and the facial mechanical pain threshold was measured. The results showed that the drug could accurately reach the trigeminal ganglion by target injection which was more effective than that by the normal injection around infraorbital foramen. Rats suffered significant mechanical allodynia in the whisker pad of the operated side from 6 d to 42 d after ION-CCI. BK(Ca) channel agonist NS1619 significantly and dose-dependently attenuated the facial mechanical allodynia and increased the facial mechanical pain threshold in ION-CCI rats 15 d after operation. Kv antagonist 4-AP was able to reduce the threshold in ION-CCI rats when facial mechanical threshold was partly recovered and relatively stable on the 35th day after operation. These results suggest that BK(Ca) channel agonist NS1619 and Kv channel antagonist 4-AP can significantly affect the rats' facial mechanical pain threshold after ION-CCI. Activation of BK(Ca) channels may be related to the depression of the primary afferent neurons in trigeminal neuropathic pain pathways. Activation of Kv channels may exert a tonic inhibition on the trigeminal neuropathic pain.
4-Aminopyridine ; administration & dosage ; Animals ; Benzimidazoles ; administration & dosage ; Constriction ; Facial Pain ; physiopathology ; Injections, Intralesional ; Kv1.4 Potassium Channel ; antagonists & inhibitors ; Large-Conductance Calcium-Activated Potassium Channels ; agonists ; Male ; Orbit ; innervation ; Pain Threshold ; physiology ; Rats ; Rats, Sprague-Dawley ; Trigeminal Ganglion ; drug effects ; Trigeminal Neuralgia ; drug therapy ; physiopathology