Cervical re-injection of indocyanine green to improve sentinel lymph node detection in endometrial cancer.

OBJECTIVES: To evaluate the role of cervical re-injection of indocyanine green (ICG) to increase the detection rate of sentinel lymph node (SLN) in patients with endometrial cancer (EC) who underwent robotic-assisted surgical staging. METHODS: We retrospectively identified consecutive EC patients undergoing robotic-assisted staging with SLN biopsy at our Institution between June 2016 and April 2020. Patients were excluded if they had open abdominal surgical approach, neoadjuvant chemotherapy, and advanced stage [International Federation of Gynecology and Obstetrics (FIGO) stage III-IV] at diagnosis. According to our SLN protocol, in case of either unilateral or no SLN detection, we performed an ipsilateral or bilateral cervical re-injection of ICG. RESULTS: In total, 251 patients meeting inclusion criteria were included in the analysis. At first injection, bilateral detection was achieved in 184 (73.3%), unilateral detection in 57 (22.7%), and no detection in 10 (4.0%) patients. Cervical re-injection was performed in 51 of 67 patients with failed bilateral mapping. After cervical re-injection, bilateral detection rate increased to 94.5% (222/235), while unilateral and no detection were 5.1% (12/235) and 0.4% (1/235), respectively. CONCLUSIONS: Our results suggest that cervical re-injection of ICG, in case of failed bilateral mapping of SLN, brings about a significant improvement in SLN detection rates, therefore reducing the number of side-specific required lymphadenectomies.

The cerebellum monitors errors and entrains executive networks.

Frontal midline θ (Fmθ) activity occurs in medial prefrontal cortices (mPFC), when expected and actual outcomes conflict. Cerebellar forward models could inform the mPFC about this mismatch. To verify this hypothesis we correlated the mPFC activation during a visuomotor tracking task (VM) with performance accuracy, in control and cerebellum-lesioned participants. Additionally, purely visual (V), motor (M) and a motor plus visual tasks (V + M) were performed. An Independent Component, with a mid-frontal topography scalp map and equivalent dipole location in the dorsal anterior cingulate cortex accounted for Fmθ. In control participants Fmθ power increased during VM, when the error level crossed a threshold, but not during V + M, M and V. This increase scaled with tracking error. Fmθ power failed to increase during VM in cerebellar participants, even at highest tracking errors. Thus, in control participants, activation of mPFC is induced when a continuous monitoring effort for online error detection is required. The presence of a threshold error for enhancing Fmθ, suggests the switch from an automatic to an executive tracking control, which recruits the mPFC. Given that the cerebellum stores forward models, the absence of Fmθ increases during tracking errors in cerebellar participants indicates that cerebellum is necessary for supplying the mPFC with prediction error-related information. This occurs when automatic control falters, and a deliberate correction mechanism needs to be triggered. Further studies are needed to verify if this alerting function also occurs in the context of the other cognitive and non-cognitive functions in which the cerebellum is involved.

Synthesis of esters of androgens with unsaturated fatty acids for androgen requiring therapy.

Androgens' metabolism and activity are gaining a more and more important role in human physiology particularly referring to aging and to neurodegenerative diseases. Androgen treatment is often required for long-lasting disorders. In order to improve their duration and effects, androgens can be administered as esters of carboxylic acids. The novelty of our research is the use of esters of androgens with specific unsaturated fatty acids, in order to reduce possible side effects particularly related to chronic pathologies with altered lipid homeostasis such as X-linked adrenoleukodystrophy and cardiovascular disorders. Thus the esters of the main androgenic substances testosterone, dihydrotestosterone (DHT) and their metabolite 5α-androstan-3α,17ß-diol were chemically obtained by coupling with different unsaturated fatty acids. To this aim, fatty acids with various degree of unsaturation and belonging to different series were selected. Specifically, oleic acid (18:1, n-9), linoleic acid (18:2, n-6), and the n-3 fatty acids, α-linolenic acid (18:3), eicosapentaenoic acid (EPA, 20:5), and docosahexaenoic acid (DHA, 22:6) were used obtaining corresponding esters with acceptable yields and good degree of purity. All the synthesized compounds were tested for their cytotoxic activities in mouse NIH3T3 and human astrocyte cell lines. The esters demonstrated good tolerability and no in vitro cytotoxic effect in both cell cultures. After these promising preliminary results, the esters will be suitable for in vivo studies in order to ascertain their pharmacokinetic characteristics and their biological effects.

The soy phytoestrogens genistein and daidzein as neuroprotective agents against anoxia-glucopenia and reperfusion damage in rat urinary bladder.

Some bladder disorders, such as obstructive bladder and hyperactivity, may be caused partly by ischemia/reperfusion injury (I/R). The neuroprotective effects of estrogens were demonstrated in in vitro studies and a great interest in soy isoflavones (genistein and daidzein) as alternative to the synthetic estrogen receptor modulators for therapeutic use has been pointed out. The aim of this study was to investigate the effect of genistein and daidzein, on rat detrusor smooth muscle contractility and their possible neuroprotective role against I/R-like condition. Whole rat urinary bladders were subjected to in vitro anoxia-glucopenia (A-G) and reperfusion (R) in the absence or presence of drugs and response to electrical field stimulation (EFS) of intrinsic nerves evaluated. Furthermore rats were treated in vivo for 1 week with the phytoestrogens and the same in vitro protocol was applied to the ex vivo bladders. Antioxidant activity of genistein and daidzein on the A-G/R model was determined by measuring malonyldialdehyde (MDA). Moreover, hormones plasma levels were determined by radioimmunoassay. Genistein and daidzein administered either in vitro or in vivo showed significant neuroprotective effect and antioxidant activity. Testosterone and 17ß-estradiol plasma levels were not modified by daidzein, while a significant decrease of testosterone in genistein treated rats was evident. Moreover both phytoestrogens significantly decreased detrusor contractions induced by EFS in a concentration-dependent manner. For being either neuroprotective and myorelaxant, genistein and daidzein could be considered a good lead for new therapeutic agents to protect the urinary bladder from hyperactivity and nerve damage.

Italian version of the cornell musculoskeletal discomfort questionnaire (CMDQ-I): Translation, cultural adaptation and validation.

BACKGROUND: Almost 25%of workers in the European Union suffer from back pain, and 23%complain of muscle pain. Sixty-two percent of workers carry out repetitive operations with their hands or arms, 46%work in painful or tired positions and 35%carry or handle loads. OBJECTIVE: This study aimed to translate, culturally adapt and validate the Italian version of the Cornell Musculoskeletal Discomfort Questionnaire (CMDQ-I). METHODS: Translation and cultural adaptation procedures followed international guidelines. Participants were recruited from among the personnel components of the Italian Air Force, who were between 18 and 65 years old. Cronbach's alpha and the intraclass correlation coefficient (ICC) were calculated to assess internal consistency and stability, respectively. The CDMQ-I was administered together with the Visual Analogic Scale (VAS), and the validity was evaluated using Pearson's correlation coefficient. RESULTS: All CDMQ-I items were either identical or similar in meaning to the original version's items. The scale was administered twice with a retest after seven to 10 days to 66 participants. Cronbach's alpha was higher than 0.761, and the ICC ranged between 0.737 and 0.952. Pearson's correlation coefficient showed positive and significant correlations (p > 0.01). CONCLUSIONS: The study produced an Italian version of the CMDQ with good reliability and validity. This scale is a useful tool to investigate the frequency and intensity of musculoskeletal disorders in various categories of workers.

Glucocorticoid receptor mRNA expression in peripheral blood mononuclear cells in high trained compared to low trained athletes and untrained subjects.

BACKGROUND: Physiological needs during prolonged exercise are a potent stimulus for the hypothalamic-pituitary-adrenal (HPA) axis. Hence, athletes undergoing daily endurance training sessions may have frequent and prolonged phases of endogenous hypercortisolism. Since chronic glucocorticoids treatment leads to down-regulation of glucocorticoid receptor alpha (GR-alpha) mRNA expression, endurance training could lead to modulation of GR expression. AIM: The aim of the study was to evaluate GR-alpha and GR-beta mRNA expressions in peripheral blood mononuclear cells and plasma cortisol, ACTH and cortisol binding globulin (CBG) concentrations at rest in subjects undergoing different training regimes. SUBJECTS AND METHODS: Nine high trained (HT) swimmers (training volume: 21.6+/-1.7 hours/week in 10-12 sessions) were compared with two age-matched control groups represented by 8 low trained (LT) runners (training volume: 6.4+/-2.6 h/week in 3-5 sessions) and 9 untrained subjects. Expression of GR was determined by RT-PCR of total RNA. Hormone levels were determined by radioimmunoassay methods. RESULTS: HT athletes showed 10 times less GR-alpha mRNA expression than the untrained subjects, while LT athletes exhibited values about twofold less than the untrained subjects. GR-beta mRNA expression was undetectable in all subjects. No differences were observed among the three groups in hormone levels. CONCLUSIONS: GR- alpha mRNA expression is repressed in proportion to the amount and frequency of the stressful stimuli due to training. Hence, this down-regulation may be a consequence of the frequent and prolonged exposure to cortisol acute elevations induced by training. GR-beta did not play an important role in inducing the down-regulation of GR-alpha mRNA expression observed.

Unlocked versus dynamic and static distal locked femoral nails in stable and unstable intertrochanteric fractures. A prospective study.

INTRODUCTION: Few clinical studies have analyzed the utility of distal interlocking screws in stable and unstable intertrochanteric fractures treated with intramedullary devices. We performed a prospective analysis comparing short unlocked versus short dynamic and short static distal locked intramedullary nails. MATERIALS AND METHODS: Nine level-II trauma centres were involved in the study. 240 patients over the age of 65 with a stable (AO/OTA 31-A1) or unstable intertrochanteric fracture (AO/OTA 31-A2) were prospectively investigated. The same type of nail was used in every patient. Patients were randomly divided into 3 groups according to the type of distal locking used. Intra-operative variables were examined and patients were followed clinically and radiographically at 1, 3, 6, 12 months postoperatively. All complications were recorded. RESULTS: A total of 212 patients completed 1 year of follow-up visits. In the Unlocking Group (UG) the operation time, blood loss, fluoroscopy time, total length of incision were significantly decreased compared to both the Dynamic Group (DG) and the Static Group (SG) (p < 0.05). Conversely, no reliable differences in intraoperative variables were noted between the Dynamic Group and the Static Group (p > 0.05). In terms of time of fracture union we found no differences among the three Groups (p > 0.05). Moreover, no cases of limb shortening >1 cm or varus collapse were detected in any group. The 3 Groups were similar in terms of HHS, SF-12 and Barthel index results at 1-year follow-up (p > 0.05). Finally, no significant differences were demonstrated across the three Groups in terms of major complications. CONCLUSIONS: This clinical study further confirms the hypothesis that short intramedullary nails do not need to be locked for stable and unstable intertrochanteric fractures.

Single opioid administration modifies gonadal steroids in both the CNS and plasma of male rats.

While morphine remains one of the most widely used opioids for the treatment of painful conditions, other opioids are also commonly employed. Because of the interactions between opioids and gonadal hormones, in particular opioid-induced hypogonadism, this study investigated the effects of widely used opioids on plasma testosterone and estradiol levels and brain testosterone levels in male rats. Animals were s.c. injected with two concentrations of morphine (5 or 10 mg/kg), fentanyl (0.05 or 0.1 mg/kg), tramadol (10 or 40 mg/kg), buprenorphine (0.05 or 0.1 mg/kg) or saline (0.7 ml/kg). Four or 24 h after treatment, the rats were deeply anesthetized to collect blood samples from the abdominal aorta and to perfuse the brains with saline. Plasma and brain hormone levels were measured by radioimmunoassay. In rats studied 4 h after treatment, all the opioids except tramadol 10 mg/kg decreased plasma testosterone in comparison with saline administration. At the same time, plasma estradiol levels were lower than control in the groups treated with the low doses of morphine, tramadol and buprenorphine, while estradiol remained at control levels in the other groups. Twenty-four hours after treatment, plasma testosterone levels were different (higher) than control in the animals treated with the low doses of morphine, fentanyl and buprenorphine. Estradiol was lower than control in the low dose groups, while the high doses did not produce any changes with respect to control. Four hours after treatment, brain testosterone was drastically decreased in all groups except buprenorphine, in which it remained at control levels. All groups returned to control levels at 24 h after treatment. In conclusion, opioids exert important effects on plasma and CNS sex hormone levels. The different magnitude and time-course of the effects of the different opiates on testosterone and estradiol levels are likely due to their different mechanism of action.

The paired box domain gene PAX5 is fused to ETV6/TEL in an acute lymphoblastic leukemia case.

The PAX5 gene, encoding the B-cell-specific activator protein, is a critical determinant of commitment to the B-lymphocyte pathway. This gene, mapped at 9p13, is juxtaposed to the immunoglobulin heavy chain (IgH) gene as a result of the t(9;14)(p13;q32), a rare but recurring translocation found in a subset of B-cell non-Hodgkin's lymphoma cases. In all of these, this translocation results in deregulated expression of the gene product because of the proximity of IgH. We present here the molecular characterization of a previously reported acute lymphoblastic leukemia case carrying a t(9;12)(q11;p13) translocation. Using 5' rapid amplification of cDNA ends PCR, a novel chimeric transcript was identified that contained the NH(2)-terminal region of PAX5 and most of the ETV6/TEL gene on 12p13. According to the fusion transcript, the resulting chimeric protein would retain the PAX5 paired-box domain and both the helix-loop-helix and DNA binding domains of TEL. Thus, it is reasonable to hypothesize that this protein could act as an aberrant transcription factor. This is the first report of PAX5 rearrangement in a human malignancy resulting in a chimeric transcript.

Total rectosigmoidectomy versus partial rectal resection in primary debulking surgery for advanced ovarian cancer.

PURPOSE: To compare in a sample of Italian patients intraoperative, perioperative complications, Quality of Life (QoL), recurrence rate and overall survival of advanced ovarian cancer (AOC) patients according to the type of surgery performed on sigma-rectum, total rectosigmoid resection (TRR) versus partial rectosigmoid resection (PRR). METHODS: From May 2004 to May 2010, consecutive patients affected by epithelial AOC (FIGO Stage III-IV) were assessed for this prospective case-control study, According to the type of colorectal surgery performed to approach rectosigmoid involvement, patients were allocated into Group A (TRR) and Group B (PRR). PRR was performed when the complete removal of disease led to a laceration <30-40% of intestinal wall circumference. RESULTS: 82 and 72 patients were included in Group A and Group B respectively. Surgical outcomes were statistically similar except hospital stay which was significantly lower in the PRR group. There was not a statistically significant difference as regarding intra-operative, perioperative and postoperative complications, even if a higher rate of major complications were recorded in TRR. An improvement in QoL's scores has been recorded in PRR's group. There was not a statistically difference concerning the optimal debulking rate (92% and 96% respectively) and 5-year Overall Survival (48% and 52% respectively). CONCLUSIONS: PRR seems to be feasible in over 40% of patients with advanced ovarian cancer and recto-sigmoid colon involvement. It is related to higher QoL and can be easily performed, without jeopardizing surgical radicality, in those cases in which conservative surgery at intestinal tract does not compromise residual tumor.

Is distal locking with short intramedullary nails necessary in stable pertrochanteric fractures? A prospective, multicentre, randomised study.

We investigated whether a proximal femoral nail can be implanted without a distal locking screw in AO/OTA 31-A1 and 31-A2 pertrochanteric stable femur fractures. A multicentre, randomised study was conducted in six level-two trauma centres in our area (Puglia, Italy). A total of 333 patients received their allocated intervention (162 in the locking group [LG] and 171 in the unlocking group [UG]) and 266 patients were included in the final analysis at 1year. Our data showed no statistically significant difference between the two groups at 1-year follow-up for ability to walk, SF-36 questionnaire results, residual pain (visual analogue scale [VAS] score) and level of overall satisfaction. There were also no statistically significant differences between groups for mortality and length of hospital stay. Conversely, the UG was associated with shorter operation and fluoroscopy times, shorter surgical incision length, and less blood loss and residual thigh pain. Pertrochanteric stable fractures (31-A1, 31-A2) can be treated successfully with intramedullary nails without distal locking, reducing patient and clinical personnel radiation exposure and sanitary costs (surgery time and screws costs).

Role of gonadal hormones in formalin-induced pain responses of male rats: modulation by estradiol and naloxone administration.

The aim of this study was to assess the possible mediation of endogenous opioids in the effects of gonadal hormones on the responses to formalin pain. We studied the effects of intracerebroventricular injection of estradiol and/or naloxone on the magnitude and time-course of the formalin-evoked behavioural and hormonal responses of intact and gonadectomized male rats. Animals were gonadectomized or left intact; on days 20 and 21 after surgery, they were intracerebroventricularly injected with 17beta-estradiol (1 microg/5 microl) or saline. On day 22, the animals received naloxone (2.5 microg/5 microl) or saline intracerebroventricularly and then, 15 min later, were subcutaneously injected with formalin (50 microl, 5%) or only pricked with a syringe needle in the dorsal hindpaw. The rats were then introduced to a testing apparatus where the formalin-induced licking, flexing and jerking of the injected limb and the other spontaneous behaviours were recorded for 60 min. At the end of the test, the animals were killed and blood was collected from the trunk. Gonadectomy and naloxone increased flexing duration independently of the other treatments. In gonadectomized rats, estrogen increased licking duration and decreased paw-jerk frequency during the first phase (0-15 min) of the formalin test. During the second phase (16-60 min), licking was increased by estrogen only in intact animals. Treatment with naloxone completely abolished all these modifications. The three measures of activity (rearing, inner and outer crossing) showed that while in sham-treated animals the gonadectomy-induced decrease in activity was completely counteracted by estrogen administration, in formalin-treated animals the gonadectomy-induced decrease was not affected by estrogen. In fact, estrogen appeared to further depress the motor activities in the formalin groups. Naloxone reversed these modifications only for outer crossing frequency, blocking the gonadectomy-induced decrease in sham-treated animals. Corticosterone plasma levels were increased by formalin only in estrogen-treated animals, independently of naloxone. In conclusion, these data indicate an important role of both male gonadal hormones and estrogen in formalin-pain responses, acting through opiate and non-opiate mechanisms.

Formalin-induced changes in adrenocorticotropic hormone and corticosterone plasma levels and hippocampal choline acetyltransferase activity in male and female rats.

Formalin (10%) induces higher levels of licking and flexing in female than in male rats, as shown in the present study. In order to ascertain the neural and hormonal modifications that accompany these behavioural differences, we determined the activity of choline acetyltransferase in the hippocampus and the levels of adrenocorticotropic hormone and corticosterone in the plasma. Two concentrations of formalin were used (50 microliters; 0.1% or 10%). Formalin was injected subcutaneously in the dorsal part of the hindpaw, and the animal's behaviour was then recorded for 60 min in a familiar open-field apparatus. Hippocampal choline acetyltransferase activity did not differ between the two genders in controls, while a significant gender difference was present in both formalin-injected groups, with higher levels in females than in males. This was the result of a decrease in males but not in females. In contrast, adrenocorticotropic hormone was increased by both formalin concentrations in females; corticosterone was not affected by treatment in either gender. Results are discussed in the light of the morphological and functional differences between the two genders in the hippocampus and in the hypothalamo-pituitary-adrenal axis.

Sex-dependent effects of formalin and restraint on c-Fos expression in the septum and hippocampus of the rat.

In the present study we have demonstrated that the same aversive stimulus induces different patterns of expression of transcription factors in the hippocampus and septum of male and female rats. We have investigated by immunohistochemistry the effects of a persistent painful stimulus and restraint stress on c-Fos expression in the hippocampus and septum of male and female rats. Subjects were randomly assigned to one of three experimental groups: (i) untreated controls, (ii) subcutaneous injection with formalin (50 microliters, 10%) in the right hindpaw, or (iii) immobilization in an adjustable restrainer. Formalin-treated and restrained animals were killed 90 min after the beginning of treatment. In both male and female rats, unilateral injection of formalin induced bilateral c-Fos expression in the hippocampus, but the number of labeled neurons was two-fold higher in females than in males. Restraint stress was not effective in c-Fos induction in the hippocampus of both sexes. In the septum, both treatments increased c-Fos, but this increase tended to be greater in males than females. Previous experiments have consistently shown that male and female rats react differently to aversive stimulation. The present findings suggest that hormonal and behavioral differences between the sexes are accompanied by genetic modifications in those brain areas involved in cognition and emotion.

Immune and neuroendocrine response to restraint in male and female rats.

A parallel study of the modification in the opioid and immunological systems induced by acute restraint (RT) was carried out in male and female rats 24 hr after the treatment. beta-Endorphin-like immunoreactivity (beta-ELI) was measured in two brain areas (ventral hypothalamus [HYP] and periaqueductal gray matter [PAG]) and in the pituitary (anterior and neurointermediate lobes), together with plasma corticosterone (C) and ACTH. Immune function was measured as mitogen-induced Interferon-gamma (IFN-gamma) production by splenocytes. RT reduced beta-ELI levels in the PAG in males and females. Plasma levels of C and ACTH did not differ from the basal levels in restrained animals. RT reduced IFN-gamma production in both sexes, but this effect was more marked in females than in males. The possible relationship between the immune and opioid system is discussed.

The role of Fbg in platelet adhesion to polymeric materials in conditions of psychological stress.

The effect of psychological stress on platelet adhesion to five polymeric materials (polyurethane, polyurethane filled with BaSO4, polyethyleneterephthalate, silicone and low-density polyethylene) was studied. The platelets were obtained from non-stressed and stressed rabbits as platelet-rich plasma (PRP) and, once washed (Pw), were suspended in different media, i.e. in platelet poor plasma (Pw-PPP), in serum (Pw-S) and in Krebs-Ringer solution (Pw-KR). Scanning electron microscopy of platelet adhesion and morphology revealed differences in the platelet activating power of the various materials. The washing procedure and resuspension in PPP generally resulted in an increased number of adherent platelets, compared with the number of platelets adherent to the same material in PRP. However, platelets washed and suspended in Pw-KR or Pw-S showed the same shape distribution as in PRP. When platelets from stressed rabbits were used, there was very strong aggregation and activation of the platelets in both PRP and Pw-PPP, independent of the chemical nature and surface structure of the material. In contrast, in Pw-KR and Pw-S (in which Fbg is absent) a general picture of single, not very modified platelets was observed. Their number and shapes changed according to the nature of the different materials. On the whole, the present results confirm our original hypothesis of a key role of the psychological condition of the blood donor and strongly indicate Fbg as the determinant factor in the pattern of platelet adhesion.

Intratympanic therapy for Ménière's disease. High-concentration gentamicin with round-window protection.

Many therapeutic options exist for the management of patients with Ménière's disease. In the last few years, the use of intratympanic gentamicin has been investigated as an alternative treatment to vestibular nerve section or labyrinthectomy. In humans, the concentration of gentamicin used for intratympanic treatment of vertigo ranges from 10 mg/mL to 40 mg/mL, and the number of doses from 2 to 14, with a total administered amount between 6 and 2.400 mg. Here lower doses of gentamicin were used, usually had the lowest incidence of hearing loss, but more injections were needed to ablate vestibular function. The purpose of this study was to evaluate the acute and chronic ototoxic effects of intratympanic high-concentration gentamicin after having obliterated the round-window niche with connective tissue in 11 subjects' ears with Ménière's disease. Intratympanic gentamicin was administered according to a predetermined and fixed schedule consisting of two doses of 0.5 mL gentamicin solution, injected once a week with a drug concentration of 80 mg/mL. The total dose of gentamicin was < or = 80 mg. The charts of the patients were surveyed in accordance with the 1995 AAO-HNS guidelines. Three patients had recurrence of vertigo between 3 and 6 months after the second injection and went on to one additional dose of gentamicin. At 2 years follow-up, 10 patients (91%) had complete and 1 (9%) substantial control of vertigo; 3 subjects (27%) had hearing decreased. Tinnitus disappeared or decreased in 3 patients (27%); eight subjects (73%) reported their aural pressure abolished or decreased. The present study demonstrates that in patients with Ménière's disease, 0.5 mL gentamicin solution, with a concentration of 80 mg/mL (total dose < or = 80 mg), injected intratympanically once a week after having obliterated the round-window niche, permits complete or substantial control of vertigo in two-thirds of cases after two doses and in all subjects after three doses. This vertigo control rate is compared to that observed after vestibular nerve section. Hearing results are not different from those with natural control, with endolymphatic sac surgery, and with vestibular nerve section.

Effects of formalin-induced pain on exploratory behaviour in rabbits.

We have used formalin to assess the long-term behavioural and hormonal effects of persistent pain in rabbits. Behaviour has been recorded over 10 min sessions both before and after 10 min, 4 and 24 hours after injection of formalin. A low dose of formalin (0.1 ml at 5%) elicited licking of the injected paw which lasted only a few minutes. Exploratory behaviour was greater than in the control (sham-injected) animals in all post-injection sessions. Following a larger dose of formalin (0.5 ml at 8%) licking occurred in all post-injection sessions, while exploration was lower than the controls only immediately after injection. Twenty-four hours after the formalin injection, testosterone levels were unaffected. Corticosterone levels increased over the course of the experiment but this increase was equal for the experimental and the control groups. Results suggest that different pain intensities and durations have opposite effects on exploratory behaviour in rabbits.

Effects of gonadal hormones and persistent pain on non-spatial working memory in male and female rats.

There are indications of a modulatory role carried out by gonadal hormones and pain in cognitive functions. We have examined this issue in male and female rats by assessing the impact of gonadectomy and persistent pain on the object recognition test. Intact and gonadectomized male and female rats were exposed to an open field (15 min) in which three objects were placed (Trial 1); the same test was repeated 2 h later (Trial 2), after the replacement of a "familiar" object with a novel one. Three days later (Day 2), the same procedure was repeated (Trial 3 and 4 with 2 h in between) but half of the animals were exposed to formalin-injection immediately before Trial 3. The latency, frequency and duration of approaching the three objects were recorded in each trial and compared by sex, gonadectomy and formalin treatment. The results showed that gonadectomized males and females had lower levels of approach to all objects and less locomotor/exploratory activity than intact animals in all experimental trials; their behaviour was not affected by repetition of the test or by pain. On Day 1, intact males showed a higher level of approach to the novel object than females. In intact males, the 2 h delay between the first and second trial failed to induce any significant modification of exploration of the novel object with respect to the familiar one, while in intact females the novel object was approached much less than the familiar one. Similarly on Day 2, the novel object was approached for a longer time by intact males than by all the other groups. In conclusion, our data show that physiological levels of circulating gonadal hormones significantly affected the performance of male but not female rats when exposed to the object recognition test.