Exploring thoracic kyphosis and incident fracture from vertebral morphology with high-intensity exercise in middle-aged and older men with osteopenia and osteoporosis: a secondary analysis of the LIFTMOR-M trial.

Our aim was to explore change in kyphosis and vertebral fracture incidence following 8 months of high-intensity resistance and impact training (HiRIT) or machine-based isometric axial compression (IAC) training in men with osteopenia and osteoporosis. HiRIT and IAC improved posture. HiRIT participants did not experience progression or incident vertebral fracture. IAC participants did experience progression and incident vertebral fracture. INTRODUCTION: The Lifting Intervention For Training Muscle and Osteoporosis Rehabilitation for Men (LIFTMOR-M) trial examined efficacy and safety of an eight-month, supervised, high-intensity progressive resistance and impact training (HiRIT) program compared with machine-based isometric axial compression (IAC) training in middle-aged and older men with low areal bone mineral density (aBMD). The primary purpose of the current work was to explore change in thoracic kyphosis and incident fracture from vertebral morphology following eight-months of HiRIT or IAC training. The secondary purpose was to explore change in clinical kyphosis measures for HiRIT, IAC and a non-randomized, matched control group. METHODS: Men (≥ 45 yrs), with low aBMD, were recruited and randomized to HiRIT or IAC, or designated control. Clinical measures of thoracic kyphosis with inclinometry were determined. Cobb angle of kyphosis and vertebral fracture assessment using the Genant semi-quantitative method were determined from lateral thoracolumbar DXA (Medix DR, Medilink, France). Per-protocol (n = 40) and intention-to-treat (n = 93) analyses were conducted. RESULTS: Forty participants (HiRIT n = 20, IAC n = 20; 66.1 ± 7.8 yrs.; lumbar spine T-score - 0.1 ± 0.8; femoral neck T-score - 1.5 ± 0.5) underwent clinical kyphosis measures and thoracolumbar DXA at baseline and follow-up. No between-group differences were detected in kyphosis change, however, within-group improvements in neutral (HiRIT - 2.3 ± 0.8°; IAC - 2.5 ± 0.8°) and 'standing tall' (HiRIT - 2.4 ± 0.8°; IAC - 2.0 ± 0.8°) postures were observed (p < 0.05). HiRIT improved Cobb angle (- 3.5 ± 1.5°, p = 0.027) from baseline. Over the 8 months, no incident vertebral fractures nor progression of prevalent vertebral fractures occurred for HiRIT participants. Five incident fractures of thoracic vertebrae occurred for IAC and one wedge fracture progressed. Ninety-three participants underwent clinical kyphosis measures at both time-points (HiRIT n = 34, IAC n = 33, control n = 26). HiRIT exhibited a reduction in 'standing tall' kyphosis compared to control (- 2.3 ± 0.6° versus 1.4 ± 0.7°, p < 0.05), but no other between-group differences were detected. CONCLUSIONS: Although there was no difference in change between intervention groups, thoracic kyphosis appeared to improve in both HiRIT and IAC with exercise exposure. HiRIT improved 'standing tall' posture in comparison to usual activities. HiRIT was not associated with vertebral fracture progression or incident vertebral fracture, but for some IAC participants there was evidence of progression of vertebral fracture severity and incident vertebral fractures, in our small sample. Larger trials are required to confirm the observations of the current work, which was exploratory in nature.

High-intensity exercise did not cause vertebral fractures and improves thoracic kyphosis in postmenopausal women with low to very low bone mass: the LIFTMOR trial.

Our aim was to assess risk of vertebral fracture during high-intensity resistance and impact training (HiRIT) for postmenopausal women with low bone mass. HiRIT did not induce vertebral fracture, as evidenced by a reduction in kyphosis following 8 months of training and a lack of change in vertebral morphology. INTRODUCTION: The LIFTMOR trial demonstrated a novel, HiRIT program notably improved bone mass in postmenopausal women with osteopenia and osteoporosis. While no clinical signs or symptoms of vertebral crush fracture were evident during the trial, anecdotal feedback suggests that concerns about safety of HiRIT in the osteoporosis demographic remain. The aim of the current work was to assess vertebral body morphology, Cobb angle, and clinical measures of thoracic kyphosis in participants in the LIFTMOR trial for evidence of vertebral fracture following 8 months of supervised HiRIT. METHODS: Participants were randomized to either 8 months of 30-min, twice-weekly, supervised HiRIT or unsupervised, low-intensity, home-based exercise (CON). Lateral thoracolumbar DXA scans (Medix DR, Medilink, France) were performed at baseline and follow-up. Cobb angle was determined, and vertebral fracture identification was performed using the semiquantitative Genant method. Clinical kyphosis measurements were performed in relaxed standing (neutral posture) and standing tall using an inclinometer and a flexicurve. RESULTS: The HiRIT group exhibited a reduction in inclinometer-determined standing tall thoracic kyphosis compared to CON (- 6.7 ± 8.2° vs - 1.6 ± 8.1°, p = 0.031). Both the HiRIT and CON groups exhibited within-group improvement in kyphosis in relaxed standing as measured by both inclinometer and flexicurve (p < 0.05). There were no changes in vertebral fracture classification in the HiRIT group post-intervention. A single, new, wedge deformity was observed for CON. CONCLUSIONS: Supervised HiRIT was not associated with an increased risk of vertebral fracture in postmenopausal women with low bone mass. Indeed, a clinically relevant improvement in thoracic kyphosis was observed following 8 months of supervised HiRIT, further supporting its efficacy as an osteoporosis intervention for postmenopausal women with low to very low bone mass.

Heavy resistance training is safe and improves bone, function, and stature in postmenopausal women with low to very low bone mass: novel early findings from the LIFTMOR trial.

UNLABELLED: The aim of the LIFTMOR (Lifting Intervention For Training Muscle and Osteoporosis Rehabilitation) trial is to determine the safety and efficacy of brief, bone-targeted, high-intensity progressive resistance training (HiPRT) with impact loading for postmenopausal women with low bone mass. Preliminary findings indicate the LIFTMOR program is safe and effective. INTRODUCTION: Despite a lack of notable efficacy, exercise guidelines for osteoporosis typically recommend moderate-intensity exercises, owing to a perceived risk of fracture from high-intensity loading. Indeed, safety concerns alone have prevented the well-recognised preferential response of bone tissue to high-intensity loads from being applied to those who stand to benefit the most. To progress from this therapeutic stalemate, a challenge to conventional wisdom was required. Our goal was to examine the safety and efficacy of HiPRT and impact loading for risk factors of osteoporotic fracture in postmenopausal women with low to very low bone mass. METHODS: Participants have been randomised to either 8 months of twice-weekly 30-min supervised HiPRT and impact loading or a low-intensity home-based exercise program of the same duration and dose. Testing at baseline and follow-up has included anthropometry; bone, muscle, and fat mass; and functional performance. RESULTS: Twenty-eight women (66.1 ± 4.8 years, mean lumbar spine T-score -2.15 ± 0.72) have completed the study. HiPRT and impact loading (n = 12) improved height (0.4 ± 0.2 cm vs -0.3 ± 0.1 cm, p = 0.003), femoral neck bone mineral density (0.3 ± 0.5 % vs -2.5 ± 0.8 %, p = 0.016), lumbar spine bone mineral density (1.6 ± 0.9 % vs -1.7 ± 0.6 %, p = 0.005), and functional performance (p < 0.05), compared to controls (n = 16). Compliance has been >87 %. There have been no injuries. CONCLUSIONS: Brief supervised HiPRT with impact loading is a safe and effective exercise therapy for postmenopausal women with low to very low bone mass.

Clinical study of therapeutic ocular surface medium for persistent epithelial defect.

PURPOSE: To investigate therapeutic ocular surface medium (TOSM), a potential physiological tear replacement therapy, for persistent epithelial defect (PED). METHODS: 11 eyes of 10 patients with PED for ≥ 2 weeks without improvement despite conventional treatment were enrolled in a prospective pilot study of TOSM over 1 month. RESULTS: Healing of the PED occurred in 3 out of the 11 eyes at 1, 2 and 4 weeks, respectively. At week 4, 2 eyes were almost healed (PED area ≤ 0.5 mm(2)). In 4 of the remaining 6 eyes, the PED area was reduced. Failure occurred in 1 case with end-stage ocular cicatricial pemphigoid and severe dry eye, and 1 patient withdrew due to a mild allergic reaction. There were no serious or irreversible side effects with TOSM. CONCLUSIONS: TOSM is a potential novel physiological therapy for PED that, unlike autologous serum, has the potential to be easily manufactured and widely available.

Treatment of traumatic corneal abrasions: a three-arm, prospective, randomized study.

PURPOSE: To compare three different treatment modalities for traumatic corneal abrasions. METHODS: We conducted a prospective, randomized, masked, three-arm clinical study of patients presenting with superficial corneal foreign bodies. Treatment modalities were: (1) pressure patching with ofloxacin ointment (patch group, PG, n = 18), (2) therapeutic contact lens with ofloxacin eye drops (contact lens group, CLG, n = 20) and (3) ofloxacin ointment alone (ointment group, OG, n = 28). Primary outcome measure was the difference of the mean corneal abrasion area between the three groups at 3 different time points (baseline, day 1 and day 7). RESULTS: A total of 66 patients were included in the study over a period of 2 years. Mean initial corneal abrasion area was 3.6 ± 3.4 mm² in the PG, 4.2 ± 4.0 mm² in the CLG and 3.7 ± 3.1 mm² in the OG (p = 0.875). Differences in corneal abrasion area at any time point were not statistically significant (abrasion area decrease from presentation to day 1 was 3.4 ± 3.3 mm² in the PG, 4.1 ± 4.0 mm² in the CLG and 3.5 ± 3.1 mm² in the OG, p = 0.789). The epithelium was healed in all patients at day 7. CONCLUSIONS: Treating traumatic corneal abrasions by pressure patching, a bandage contact lens or ointment alone was equal in reducing the abrasion area or reducing pain. According to our results the treatment of choice for traumatic abrasions may be adapted to the needs and preferences of the patient.

Epstein-Barr virus, B cell lymphoproliferative disease, and SCID mice: modeling T cell immunotherapy in vivo.

Epstein-Barr virus (EBV)-associated post-transplant lymphoproliferative disease (PTLD) arises in up to 10% of organ transplant recipients and is fatal in ∼50% of cases. PTLD can be modeled in SCID mice using EBV+ve human B lymphoblastoid cell lines (BLCLs), and the current study investigated intraperitoneal (ip) inoculation of such animals in experiments which assessed the effect of EBV-specific cytotoxic T lymphocytes (CTLs) and cytokines on PTLD growth. Ip transfer of one dose of autologous CTLs, or CD8-enriched T cells, into ip BLCL-inoculated animals significantly delayed tumor development (P = 0.001) and prevented tumor formation in a significant proportion (40%) of mice (P = 0.001). A combination of interleukin (IL)2, 7, and 15 conditioning of CTLs prior to ip injection significantly delayed ip BLCL-derived tumor formation in vivo when compared to CTLs expanded in vitro using only IL2 (P = 0.04) and prevented tumor outgrowth in a significant proportion (60%) of mice (P = 0.02). Daily ip IL2 dosing of ip CTL-inoculated mice significantly delayed tumor development in vivo (P = 0.004) and prevented tumor outgrowth in a significant proportion (78%) of mice (P = 0.02) when compared to animals dosed with vehicle only. In SCID mice, autologous CTLs, and CD8-enriched T cells, have significant capacity to hinder development of PTLD-like tumors. Whilst studies are needed to delineate the role of cytokine conditioning and CD4-enriched T cells, the results suggest that IL2 plays a key role in supporting CTL funtion in vivo.

Characterization of cerebrospinal fluid monoamine metabolites in peripubertal chimpanzees (Pan troglodytes).

BACKGROUND: Assessment of cerebrospinal (CSF) monoamine metabolites 5-hydroxyindoeacetic acid (5-HIAA) and homovanillic acid (HVA), and the serotonin precursor tryptophan (TRP), in chimpanzees may help in understanding the neurobiology underlying aggressive, impulsive behavior in humans and non-human primates. METHODS: Two CSF samples were obtained from 11 peripubertal chimpanzees 8 months apart and were assayed for monoamine metabolite and TRP concentrations. RESULTS: Substantial inter-individual stability was observed for 5-HIAA (n = 11; r = 0.83, P < 0.001) and HVA (r = 0.91, P < 0.001). Females had significantly higher concentrations of 5-HIAA compared to males (F(1,8) = 7.31; P < 0.05). Levels of 5-HIAA (r = -0.62, P < 0.05), HVA (r = -0.86, P < 0.001) and TRP levels (r = -0.67; P < 0.05) decreased with age. CONCLUSION: Close parallels were observed between chimpanzees and humans with respect to absolute levels, sex effects, ontogeny, and 5-HIAA-HVA correlations, supporting the potential utility of the measures in understanding relationships between monoamine functioning and behavior in chimpanzees and humans.

Acanthamoeba keratitis in Australia: demographics, associated factors, presentation and outcomes: a 15-year case review.

PURPOSE: To report the demographics, frequency of potential predisposing factors, presentation and outcomes of Acanthamoeba keratitis (AK) at a quaternary eye hospital in Sydney, Australia over a 15-year period. METHODS: A retrospective review of all patients diagnosed with AK at the Sydney Eye Hospital, Sydney, Australia between January 2002 and December 2016 was conducted. RESULTS: A total of 52 patients with AK at the quaternary referral hospital in Sydney, Australia, between January 2002 and December 2016, were included. The most commonly documented potential predisposing factors were contact lens wear (83%) and organic trauma (10%) in the non-contact lens wearers. An initial misdiagnosis of herpetic eye disease was made in 37% of patients. The presenting clinical features in order of frequency included; punctate epitheliopathy in 65% (n = 34), perineural infiltrate 46% (n = 24), stromal infiltrates 46% (n = 24), anterior uveitis 39% (n = 20), epithelial defect 35% (n = 18), limbitis 31% (n = 16), pseudo-dendrite 19% (n = 10), and ring infiltrate 4% (n = 7). Twenty-seven of the patients completed their follow-up at the Sydney Eye Hospital, improving their vision from 1.02 logMAR at presentation to 0.57 logMAR at last follow-up. Thirty-nine complications developed in 32 eyes and included corneal scarring and vascularisation, three patients experienced recurrences of AK and one patient developed a late-onset scleritis. CONCLUSION: In Australia, AK occurred predominantly in contact lens wearers with typical clinical features including epitheliopathy and perineural infiltrates. The patient demographics, frequency of potential predisposing factors and clinical presentation of AK were similar to case series from the UK and New Zealand.

Interventions for recurrent corneal erosions.

BACKGROUND: Recurrent corneal erosion is a common cause of disabling ocular symptoms and predisposes the cornea to infection. It may follow corneal trauma. Measures to prevent the development of recurrent corneal erosion following corneal trauma have not been firmly established. Once recurrent corneal erosion develops simple medical therapy (standard treatment) may lead to resolution of the episode. However some patients continue to suffer when such therapy fails and once resolved further episodes of recurrent erosion may occur. A number of treatment and prophylactic options are then available but there is no agreement as to the best option. OBJECTIVES: To assess the effectiveness and safety of prophylactic and treatment regimens for recurrent corneal erosion. SEARCH STRATEGY: We searched CENTRAL, MEDLINE, EMBASE and LILACS in June 2007. The NRR was searched in April 2005. We also contacted researchers in the field. SELECTION CRITERIA: We included randomised and quasi-randomised trials that compared a prophylactic or treatment regimen with another prophylaxis/ treatment or no prophylaxis/ treatment for patients with recurrent corneal erosion. DATA COLLECTION AND ANALYSIS: Both authors independently extracted data and assessed trial quality. We contacted study authors for additional information. MAIN RESULTS: Five randomised and one quasi-randomised controlled trial were included in the review. The trials were heterogenous and of poor quality. Safety data presented were incomplete. For the treatment of recurrent corneal erosion there was limited evidence that oral tetracycline 250 mg twice daily for 12 weeks or topical prednisolone 0.5% four times daily for one week or both in addition to standard treatment; and excimer laser ablation in addition to mechanical debridement may be effective. Therapeutic contact lens wear was inferior to lubricant drops and ointment in abolishing the symptoms of recurrent corneal erosion and had a high complication rate. For prophylaxis of further episodes of recurrent corneal erosion there was no difference in the occurrence of objective signs of recurrent erosion between hypertonic saline ointment versus tetracycline ointment or lubricating ointment. Lubricating ointment at night in addition to standard treatment following traumatic corneal abrasion (erosion) caused by fingernail injury to prevent recurrence led to increased symptoms of recurrent corneal erosion compared to standard therapy alone. AUTHORS' CONCLUSIONS: Well-designed masked randomised controlled trials using standardised methods are needed to establish the benefits of new and existing prophylactic and treatment regimes for recurrent corneal erosion.

Legeais BioKpro III keratoprosthesis implantation: long term results in seven patients.

AIMS: The long term results of the Legeais BioKpro III keratoprosthesis are presented for seven patients with severe corneal scarring. METHODS: The study took place at Moorfields Eye Hospital, London. Patients had either end stage ocular surface disease or corneal opacification after multiple failed graft surgery, with the potential for significant visual improvement. After insertion the device was covered with a conjunctival flap or buccal mucous membrane graft, which was later opened to expose the optic. The outcome measures were vision, complications, and retention of the device. RESULTS: The BioKpro III was inserted into seven patients with severe corneal scarring: ocular cicatricial pemphigoid, measles keratitis, thermal injury, Stevens-Johnson syndrome, aniridia, chemical injury, and congenital rubella. The follow up was 18-48 months. The keratoprosthesis failed in six, because of extrusion occurring 2-28 months postoperatively. Retroprosthetic membranes occurred in three patients, and endophthalmitis in one. Vision improved from hand movements to 6/12 in the only patient who retained the KPro; however he was troubled by mucus accumulation on the optic. CONCLUSIONS: The one success has been in a patient with thermal burns. The remaining results have been poor, with the KPro extruding in six of the seven patients.

Effects of chronic social separation on cardiovascular disease risk factors in female cynomolgus monkeys.

A lack of social support is associated with increased risk of coronary heart disease morbidity and mortality in human beings. Similarly, chronic social separation (single cage housing) potentiates atherosclerosis in female monkeys. Under the hypothesis that autonomic arousal and/or ovarian impairment may mediate this effect (as both are associated with increased atherosclerosis), heart rate and luteal phase plasma progesterone concentrations were measured in 12 female cynomolgus monkeys that were first socially housed, then individually housed, and finally returned to their original social groups. Afternoon heart rates increased during social separation compared to the social groupings (P < 0.001). Increased heart rates could not be explained by activity levels, which were lower during social separation than in social groupings (P < 0.001). Ovarian function (i.e. luteal-phase progesterone concentrations) was not influenced by housing condition. Single caging reduced the extent of social signaling, even though animals were in visual and auditory contact. Rates of affiliative behaviors increased and time spent alone decreased in post-reunion social groups compared to pre-separation social groups (P's < 0.01). The results indicate that chronic social separation in this group-living species may exacerbate atherosclerosis via altered autonomic activity, as evidenced by higher heart rates during social separation.

Alterations in T lymphocyte subpopulations associated with renal allograft rejection.

The peripheral blood OKT3 (total T), OKT4 (T helper/inducer), and OKT8 (T suppressor/cytotoxic) cells were determined by flow cytometry on twenty consecutive recipients of HLA-nonidentical cadaveric renal allografts. The absolute number of cells in all three populations decreased significantly posttransplantation, but no differences were found between patients experiencing rejection and those in quiescence. An OKT4/OKT8 ratio of greater than or equal to 1.7, either pretransplant or posttransplant, uniformly identified patients who subsequently experienced rejection. However, an OKT4/OKT8 ratio of less than 1.7 did not identify patients with a low risk of rejection. Pretransplant splenectomy was performed in 6 of 7 patients who rejected despite a low ratio. Serial monitoring of the OKT4/OKT8 ratio posttransplantation determined that an increase in the ratio of greater than or equal to 0.5 was a sensitive (81%) and specific (91%) indicator of a rejection episode. Graft survival was improved in patients with a high posttransplant OKT4/OKT8 ratio. These results indicate that the balance of helper and suppressor cell function may be of critical importance to the fate of an allograft, and that the alterations in this balance can be used to assist in the clinical management of allograft recipients.

An electrophysiological and histological study of trypsin induced demyelination.

Ten-microliters quantities of trypsin or saline were injected into rat tibial nerve and the physiological and histological changes evaluated and compared to the focal demyelinating lesions induced by intraneural injection of rabbit EAN serum and proteinase K. The injection of trypsin produced progressive conduction block that was maximal on day 4, and a slowing of motor nerve conduction. Early retraction of myelin at paranodes, vesicular change, and macrophage stripping of myelin from nerve axons were seen on histological examination. At day 4, the first groups of completely demyelinated axons were seen, typically in a perivascular distribution. These changes were similar to those seen in the positive controls and thus support the postulate that proteolytic enzymes from macrophages--the dominant cellular species within the demyelinating lesion, play a central role in degradation of the myelin sheath in demyelinating diseases.

Surgically induced necrotizing scleritis in a patient with ankylosing spondylitis.

We present the case of a 75-year-old man with ankylosing spondylitis who developed surgically induced necrotizing scleritis (SINS) more than 3 years after uneventful extracapsular cataract extraction and posterior chamber intraocular lens implantation. The patient presented with a painful eye and increasing vertical diplopia. To our knowledge, neither the association of SINS and ankylosing spondylitis nor vertical diplopia as its presenting complaint has been described.

Behavioral responses to ovariectomy and chronic anabolic steroid treatment in female cynomolgus macaques.

A pilot study was conducted to investigate the effects of ovariectomy on rates of aggressive and affiliative behavior, as well as body size, in 38 young adult female cynomolgus monkeys (Macaca fascicularis) living in isosexual social groups of four to five animals. In addition, we assessed the effects of nandrolone decanoate (an anabolic steroid used for postmenopausal hormone replacement therapy) on indices of aggression, submission, and body size. Animals were randomized into three experimental conditions: 1) sham ovariectomized, untreated (SHAM); 2) ovariectomized, untreated (OVX); and, 3) ovariectomized, treated with nandrolone decanoate for 24 months (NAN). Each individual was observed for 10 min, one to two times per month, and all instances of agonistic and affiliative behavior were recorded by means of focal animal sampling. Ovariectomized, untreated animals exhibited a two- to threefold increase in aggression compared to SHAM or NAN animals; F(2, 32) = 4.09, p = 0.026; however, the expression of prosocial or affiliative behaviors as measured by rates of grooming and initiating friendly behavior was unaffected. At an i.m. dose of 25 mg every 2 weeks, nandrolone decanoate caused a 60% increase in body weight of the animals compared to untreated intact and ovariectomized animals, F(2, 31) = 161.57, p < 0.0001.

Scent-marking and cortisol response in the small-eared bushbaby (Otolemur garnettii).

Among prosimians, some types of scent-marking may serve as displacement activities that reduce physiological arousal in stressful situations. Type and frequency of scent-marking was measured for 22 male small-eared or Garnett's bushbabies (Otolemur garnettii) exposed to a novel open field environment, with and without novel objects. Rates of foot rubbing, chest rubbing, urine washing, flank rubbing, and ano-genital marking were measured. Foot and chest rubbing constituted 92.5% of responses. Type and frequency of scent-marking was compared to the magnitude of the animals' cortisol responses in a separate test of restraint stress. Only foot and chest rubbing were systematically related to cortisol levels. The animals that performed these behaviors more in the novel environment also exhibited lower cortisol responses to restraint stress. These results suggest that bushbabies that characteristically employ behavioral coping strategies have a reduced physiological response to psychological stressors.

Continence following electrical stimulation and EMG biofeedback in a teenager with imperforate anus.

A teenage boy with repaired high imperforate anus relied on daily enemas for social continence. After treatment with low intensity transcutaneous electrical stimulation and electromyographic biofeedback home programs, he achieved improved fecal continence requiring only one enema per month.

Adenosine A1 receptors in mouse pontine reticular formation modulate nociception only in the presence of systemic leptin.

Human obesity is associated with increased leptin levels and pain, but the specific brain regions and neurochemical mechanisms underlying this association remain poorly understood. This study used adult male C57BL/6J (B6, n=14) mice and leptin-deficient, obese B6.Cg-Lep(ob)/J (obese, n=10) mice to evaluate the hypothesis that nociception is altered by systemic leptin levels and by adenosine A1 receptors in the pontine reticular formation. Nociception was quantified as paw withdrawal latency (PWL) in s after onset of a thermal stimulus. PWL was converted to percent maximum possible effect (%MPE). After obtaining baseline PWL measures, the pontine reticular formation was microinjected with saline (control), three concentrations of the adenosine A1 receptor agonist N(6)-p-sulfophenyladenosine (SPA), or super-active mouse leptin receptor antagonist (SMLA) followed by SPA 15 min later, and PWL was again quantified. In obese, leptin-deficient mice, nociception was quantified before and during leptin replacement via subcutaneous osmotic pumps. SPA was administered into the pontine reticular formation of leptin-replaced mice and PWL testing was repeated. During baseline (before vehicle or SPA administration), PWL was significantly (p=0.0013) lower in leptin-replaced obese mice than in B6 mice. Microinjecting SPA into the pontine reticular formation of B6 mice caused a significant (p=0.0003) concentration-dependent increase in %MPE. SPA also significantly (p<0.05) increased %MPE in B6 mice and in leptin-replaced obese mice, but not in leptin-deficient obese mice. Microinjection of SMLA into the pontine reticular formation before SPA did not alter PWL. The results show for the first time that pontine reticular formation administration of the adenosine A1 receptor agonist SPA produced antinociception only in the presence of systemic leptin. The concentration-response data support the interpretation that adenosine A1 receptors localized to the pontine reticular formation significantly alter nociception.