Social stress as a trigger for depressive-like behavior and persistent hyperalgesia in mice: study of the comorbidity between depression and chronic pain.

BACKGROUND: There is great comorbidity and similarity between chronic pain and major depressive disorders. We have recently shown that 10 days of social defeat stress (SDS) induces hyperalgesia regardless depressive-like behavior in mice. Here we aimed to investigate whether social stress predisposes to chronic pain and, inversely, whether chronic pain predisposes to stress-induced depression. METHODS: Firstly, we used the 10 days SDS paradigm in mice followed by a mild protocol of repetitive inflammatory stimulus to evaluate if SDS would predispose to persistent hyperalgesia development. Secondly, we used the intense protocol of repetitive inflammatory stimulus followed by a subthreshold SDS to evaluate if persistent hyperalgesia would predispose to depressive-like behavior of social avoidance. RESULTS: Our results showed that SDS predispose to chronic pain, since stressed mice injected with PGE2 for 7 days (mild protocol), stimuli normally not sufficient to trigger chronic pain, showed persistent hyperalgesia. Also, we showed that persistent hyperalgesia induced by repetitive inflammatory stimuli predispose to long-lasting depressive-like behavior of social avoidance induced by subthreshold SDS. LIMITATIONS: We did not analyze molecular mechanism associated with chronic pain and depressive-like behavior induced by SDS. However, we hypothesized that SDS and 14 days of PGE2 would generate neuroplasticity on brain areas shared by chronic pain and depression, predisposing to pain chronification and depressive-like behavior, respectively. CONCLUSIONS: We can conclude social stress as a key and a common factor for chronic pain and depression. We can also conclude that SDS predisposes to chronic pain and, inversely, chronic pain predisposes to depressive-like behavior.

Therapeutic and Preventive Effect of Voluntary Running Wheel Exercise on Social Defeat Stress (SDS)-induced Depressive-like Behavior and Chronic Pain in Mice.

Major depressive disorders (MDD) and chronic pain (CP) affect significant portion of the world's population and have high comorbidity rate. Social defeat stress (SDS) model was standardized in mice and can trigger depressive-like behavior and chronic pain. Based especially on clinical trials showing an effective preventive and therapeutic effect of physical exercise on CP and symptoms associated with MDD, this study aimed to investigate if the voluntary running wheel exercise can exert these effects in mice submitted to the 10-day SDS protocol, using fluoxetine as positive control. For this, we ran two set of experiments: in the first set mice started performing voluntary running wheel exercise after submitted to SDS and, in the second set, mice performed voluntary running wheel exercise before and during SDS. Mechanical and chemical hyperalgesia was analyzed through electronic von Frey and capsaicin test, respectively. Depressive-like behavior was assessed through social interaction test. Our results showed that the voluntary running wheel exercise was more effective than fluoxetine reversing the SDS-induced persistent hyperalgesia and both, fluoxetine and voluntary running wheel exercise, was effective reversing SDS-induced social avoidance. Also, voluntary running wheel exercise is an effective tool preventing both hyperalgesia and social avoidance induced by SDS. To the best of our knowledge, this was the first study using physical exercise as a therapeutic and preventive tool for chronic pain and depressive-like behavior simultaneously induced by social stress.

Anti-inflammatory effects of propranolol in the temporomandibular joint of female rats and its contribution to antinociceptive action.

BACKGROUND: ß-Blockers reduce temporomandibular joint (TMJ) pain. We asked whether they also reduce TMJ inflammation and, if so, whether this anti-inflammatory effect contributes to its analgesic action. METHODS: We measured many parameters of the inflammatory response after co-administration of the ß-blocker propranolol with the inflammatory agent carrageenan in the TMJ of female rats. We also hypothesized that the activation of ß-adrenoceptors in the TMJ induces nociception mediated, at least in part, by the inflammatory response. To test this hypothesis, we examined the nociceptive response induced by the activation of the ß-adrenoceptors in the TMJ in female rats pretreated with thalidomide and fucoidan. RESULTS: We found that the co-administration of propranolol with carrageenan in the TMJ of female rats significantly reduced several parameters of the inflammatory response induced by carrageenan such as plasma extravasation, neutrophil migration and the release of the pro-inflammatory cytokines TNF-α, IL-1ß and CINC-1. Furthermore, the injection of the ß-adrenergic receptor agonist isoproterenol in the TMJ induced nociception that was significantly reduced by thalidomide, fucoidan and by the co-administration of propranolol but not of the α-adrenergic receptor antagonist phentolamine. CONCLUSIONS: Propranolol has anti-inflammatory effects that contribute to its antinociceptive action in the TMJ of females. SIGNIFICANCE: ß-Blockers have an anti-inflammatory effect on temporomandibular joint (TMJ) that contributes to its analgesic effect. The results of this work suggest that ß-blockers can be used to treat the painful conditions of TMJ, especially when they are associated with an inflammatory process.

Classical aversive conditioning induces increased expression of mature-BDNF in the hippocampus and amygdala of pigeons.

The expression of brain-derived neurotrophic factor (BDNF), which is found in the pro-BDNF, truncated-BDNF and mature-BDNF isoforms, changes with learning. Mature-BDNF shows a peak of late expression in the hippocampus that is involved in the persistence of aversive memory in rodents. However, the role of BDNF in the hippocampal synaptic mechanisms involved in the classical conditioning aversive memory in birds still needs clarification. This study investigated the late expression of BDNF in the hippocampus and amygdala of pigeons trained with tone-shock conditioning and the effects of intra-hippocampal infusion of anisomycin (Ani) in these changes. Seven days after implantation of intra-hippocampal microcannulae, adult pigeons trained with three tone-shock pairings were assigned to one of three groups: Conditioning and Ani (CondANI), Conditioning and saline vehicle (CondSAL) and Conditioning only (Cond). NAIVE group had no treatment or conditioning. Homogenates of tissues from the hippocampus and amygdala, obtained 12h after training, were used to determine the content of mature-BDNF, truncated-BDNF and pro-BDNF using Western blotting. Higher values for mature-BDNF than for truncated- and pro-BDNF content were seen in the hippocampus of Cond and CondSAL birds, but not in the hippocampus of CondANI or NAIVE birds (p<0.05). The values of mature-BDNF in the amygdala of all the three conditioned groups were higher than those observed for truncated- and pro-BDNF (p<0.05), which indicates that the activation of this protein in the amygdala was not affected by the infusion of Ani in the hippocampus. The data indicate that the tone-shock conditioning induced the activation of molecular pathways of BDNF in the hippocampus and amygdala of the pigeons. The decreases in the content of truncated- and pro-BDNF isoforms found in conditioned pigeons may suggest cleavage mechanisms induced by the training. Our data confirm previous observations of rodent studies and extend these observations to pigeons, revealing that, in spite of the anatomical differences between the hippocampus of rodents and pigeons, there are functional and molecular mechanisms that are conservative between the species.

The antidepressive effect of the physical exercise correlates with increased levels of mature BDNF, and proBDNF proteolytic cleavage-related genes, p11 and tPA.

Clinical studies show an evident antidepressive effect of physical exercise and animal research corroborate such evidence. However, the neurobiological mechanisms underlying the antidepressive effect of exercise are not completely understood. Notwithstanding, it is known that exercise increases brain-derived neurotrophic factor (BDNF) expression in the hippocampus similarly to antidepressant drugs. BDNF is synthesized as a precursor molecule that undergoes a proteolytic cleavage to generate either a mature or a truncated isoform. Precursor and mature BDNF are assumed to elicit opposing biological effects in neuroplasticity. In the present study we investigated the effect of voluntary physical activity on precursor and mature brain-derived neurotrophic factor levels and on proBDNF cleavage related genes, p11 and tissue plasminogen activator (tPA), as well as the antidepressive and cognitive effects of voluntary physical activity. Mice had access to mobile or locked running wheels for 28 days and were submitted to forced-swim, tail suspension and water maze tests. Their hippocampi were dissected and analyzed by Western blot and real time RT-PCR. Voluntary physical activity, but not locked wheel exposure, induced a robust increase in hippocampal mature BDNF protein levels, as well as in p11 and tPA mRNA expression; and also promoted antidepressive effects and improved learning, when compared with sedentary mice. On the other hand, there were no significant differences between any groups in the expression of precursor or truncated isoforms of BDNF. Our data suggest that the antidepressive effect of the physical exercise may depend, at least in part, on changes in BDNF post-translational processing.

Multiple basaloid follicular hamartomas associated with acrochordons, seborrhoeic keratoses and chondrosarcoma.

Basaloid follicular hamartoma is an uncommon neoplasm with distinctive histopathological findings. It presents as four distinctive clinical forms: a solitary papule, a localized plaque of alopecia, a localized linear and unilateral type, and generalized papules with associated alopecia and myasthenia gravis. Histologically, basaloid follicular hamartomas are characterized by thin branching strands and thick cords of basaloid or squamoid cells extending from a follicle into a loose, fibrillar, fibrocytic or mucinous connective tissue stroma. We report a case of long-standing, generalized basaloid follicular hamartomas associated with acrochordons, seborrhoeic keratoses, and a history of chondrosarcoma. In general, solitary tumours are sporadic; multiple tumours are inherited and frequently associated with a syndrome. Further surveillance is warranted to determine if the association of multiple basaloid follicular hamartomas and chondrosarcoma constitutes an inherited syndrome.

Erythema dyschromicum perstans: a case report and review.

Erythema dyschromicum perstans (EDP) is an acquired ashy dermatosis characterized by patches of blue-gray pigmentation over the trunk, extremities, and neck. These pigmentary changes may become chronic and disfiguring. At present, the etiology of EDP remains unclear, and there is no single established therapy. We describe a 21-year-old Hispanic man with extensive patches of EDP who improved with oral corticosteroid therapy.

Solitary nodule of the great toe.

We describe a 21-year-old woman with a subungual exostosis exhibiting both skin and nail findings. The patient presented with a firm, flesh-colored, nontender, subungual nodule in the distal nail bed of the great toe. Radiographic examination revealed focal calcification of the nodule, with direct communication to the underlying phalanx. Subungual exostosis should be considered in the differential diagnosis of any digital mass. Surgical excision, followed by curettage of the base, is the treatment of choice.

Colon carcinoma cutis: a case report.

The occurrence of cutaneous metastasis from colon cancer is rare especially when located on the extremities. Cutaneous metastasis typically signifies widespread disease and poor prognosis. Although uncommon, carcinoma cutis must be considered in any patient with a history of carcinoma who presents with a new skin eruption. Diagnostic biopsy is essential, inasmuch as the appearance of these lesions is not distinctive. We present a patient with known colon cancer and the new onset of papules on her right lower extremity.

The dermatologist in military operations.

The military dermatologist has a specific and significant role in military operations--in time of war as well as in peace. Many dermatologists are unfamiliar with the impact that our specialty and cutaneous disease has upon the ability of the military to fulfill the missions, duties, and responsibilities assigned by our government. This article highlights a few of the recent or ongoing types of military operations in which our specialty plays a prominent part.

Costal fringe.

Costal fringe consists of a bandlike pattern of venous telangiectases along the anterolateral costal margins. It is a common and easily recognized entity, usually seen in elderly men. Association with underlying disease is not well established. To assess the frequency of costal fringe in a healthy young adult population, we examined 1523 active duty Air Force personnel (1203 men and 320 women) between the ages of 17 and 34 years. All subjects were human immunodeficiency virus seronegative; none had known hyperestrogenic or other disease states. Costal fringe was present in only three individuals, all men, a frequency of 0.2%. Costal fringe is a rare finding in healthy young adults.