Endovascular catheter-delivered photodynamic therapy in an experimental response to injury model

Background The effectiveness of local endovascular photodynamic therapy (PDT) in preventing tissue hyperplasia was evaluated in a vascular injury model.Methods Standardized unidirectional arterial injury with a directional atherectomy catheter was performed in porcine arteries (n=180). Animals (n=72) were randomly allocated to unidirectional injury only (Group 1), injury followed by drug delivery of photosensitizer with a porous balloon (Group 2), or by local exposure to monochromatic light (Group 3). In Group 4, injury was followed by local drug delivery of photosensitizer and subsequent exposure to light (PDT). Up to 21 days after treatment, all experimental vessels were excised, fixed and processed for histology, immunohistochemistry and transmission electron microscopy.Results After vascular injury an inflammatory and myoproliferative response was observed in Groups 1, 2 and 3 (mean tissue hyperplasia/media ratio 1.0±0.5 at 21 days; area tissue hyperplasia: 1.57±0.9 mm²). Proliferation in injured vascular segments (Group 1–3) reached a maximum at 7 days, with 6%. Only in Group 4, injury followed by photodynamic therapy, was there no significant vascular response (mean tissue hyperplasia/media ratio 0.3±0.2; area tissue hyperplasia: 0.1±0.05 mm² p<0.001, proliferating cells 0.3%).Conclusion Vascular response after unidirectional injury was suppressed only by endovascular photodynamic therapy.     

The response of brainstem neurons to chemical activation of gastric sensory receptors

Sensory receptors have been identified in the proximal stomach of the cat that respond to mechanical and chemical stimuli. The neurotransmitters or neuromodulators that underlie the brainstem excitatory responses initiated by gastric mechanical and chemical stimuli may provide a very important link in the control of obesity.     

Some rat sensory neurons in culture express characteristics of differentiated pain sensory cells.

Sensory neurons were dissociated from trigeminal ganglia or from dorsal root ganglia of rats, grown in culture, and examined for expression of properties of pain sensory cells. Many sensory neurons in culture are excited by low concentrations of capsaicin, reportedly a selective stimulus for pain sensory neurons. Many are excited by bradykinin, sensitized by prostaglandin E2, or specifically stained by an antiserum against substance P. These experiments provide a basis for the study of pain mechanisms in cell culture.     

Tonic modulation of spinal hyperexcitability by the endocannabinoid receptor system in a rat model of osteoarthritis pain

Objective

To investigate the impact of an experimental model of osteoarthritis (OA) on spinal nociceptive processing and the role of the inhibitory endocannabinoid system in regulating sensory processing at the spinal level.

Methods

Experimental OA was induced in rats by intraarticular injection of sodium mono‐iodoacetate (MIA), and the development of pain behavior was assessed. Extracellular single‐unit recordings of wide dynamic range (WDR) neurons in the dorsal horn were obtained in MIA‐treated rats and saline‐treated rats. The levels of endocannabinoids and the protein and messenger RNA levels of the main synthetic enzymes for the endocannabinoids (N‐acyl phosphatidylethanolamine phospholipase D [NAPE‐PLD] and diacylglycerol lipase α [DAGLα]) in the spinal cord were measured.

Results

Low‐weight (10 gm) mechanically evoked responses of WDR neurons were significantly (P < 0.05) facilitated 28 days after MIA injection compared with the responses in saline‐treated rats, and spinal cord levels of anandamide and 2‐arachidonoyl glycerol (2‐AG) were increased in MIA‐treated rats. Protein levels of NAPE‐PLD and DAGLα, which synthesize anandamide and 2‐AG, respectively, were elevated in the spinal cords of MIA‐treated rats. The functional role of endocannabinoids in the spinal cords of MIA‐treated rats was increased via activation of cannabinoid 1 (CB₁) and CB₂ receptors, and blockade of the catabolism of anandamide had significantly greater inhibitory effects in MIA‐treated rats compared with control rats.

Conclusion

Our findings provide new evidence for altered spinal nociceptive processing indicative of central sensitization and for adaptive changes in the spinal cord endocannabinoid system in an experimental model of OA. The novel control of spinal cord neuronal responses by spinal cord CB₂ receptors suggests that this receptor system may be an important target for the modulation of pain in OA.

     

Effect of age on cytokine response in an experimental model of osteomyelitis

To study the effect of age on cytokine response in an experimental model of osteomyelitis. Forty adult male Wistar rats received a stainless steel needle, intramedullarly in the left tibia. Young rats (3 months old) and old rats (22 months old) were allotted in: Group A: Sterile implant. Group B: Sterile implant + slime producing S. aureus. Rats were sacrificed 9 weeks after surgery. Determinations: Cytokines (ELISA) in blood and in tibia extract and the number of bacteria in tibia and implant. The Wilcoxon, Mann–Whitney U tests were used (P ≤ 0.01 significant). Infection was detected in every old rat receiving S. aureus, and in 7 of 10 young rats. In blood: prior to surgery, old rats presented higher IL-2 and lower IL-4 levels. Surgery alone did not induce significant changes in old rats; surgery + S. aureus induced significant increases of IL-2 and IL-10 in young rats, and of IL-6 in old rats. Tibia analysis S. aureus group showed increased levels of: IL-10 in young rats, and IL-1β in old rats. In experimentally induced osteomyelitis, significant differences were observed in cytokine response with regard to age.     

Severity of knee pain does not predict a better response to an antiinflammatory dose of ibuprofen than to analgesic therapy in patients with osteoarthritis

OBJECTIVE: To determine whether greater pain intensity at initiation of treatment predicted better response to ibuprofen than to acetaminophen in subjects with knee osteoarthritis (OA). METHODS: Data from 182 patients with knee OA who had taken part in a 4 week randomized, double blind, parallel comparison of 4,000 mg/day acetaminophen vs either 1,200 or 2,400 mg/day ibuprofen were reanalyzed using Pearson correlation coefficients for baseline pain severity, treatment assignment, and treatment response. Pain measures were visual analog scales for overall pain, resting pain, and walking pain. Baseline pain severity was divided into low, medium, and high tertiles, and treatment related differences in pain response were sought with pairwise t tests. Two-factor analysis of variance (ANOVA) models were used to seek interactions between baseline pain severity and treatment group, which would indicate differential drug treatment responsiveness. RESULTS: Greater baseline pain predicted greater pain relief with all 3 treatments. Patients with a high level of baseline rest pain appeared to respond better to ibuprofen 2,400 mg/day than to the other treatments, but this difference was not evident after correction for multiple statistical tests. ANOVA did not reveal significant differences in response to the 3 treatments or a significant interaction. CONCLUSION: Our data suggest that acetaminophen and ibuprofen are comparably effective in treating knee OA pain, even when the pain is severe.     

The distribution of spinal and vagal sensory neurons that innervate the esophagus of the cat.

The distribution of spinal and vagal neurons that convey sensory information from the distal smooth muscle esophagus is poorly documented. Therefore, sensory cell bodies were retrogradely labeled by injecting fast blue into the striated and smooth muscle of the esophageal body and into the lower esophageal sphincter of the cat. The maximum distribution of spinal sensory neuron labeling was found in the following dorsal root ganglia: C1-T8 (striated muscle); C5-L2 (smooth muscle), and T1-L3 (lower esophageal sphincter). Vagal sensory neurons in the nodose ganglion were found to have a crude topographic layout. The total number of vagal sensory neurons labeled by injection into the three esophageal areas was greater than the number of spinal neurons labeled (809.7 +/- 166.1 vs. 328.9 +/- 53.4; mean +/- SEM; n = 12; P less than 0.005). It is concluded that spinal sensory neurons of the esophagus are segmentally arranged. Accordingly, each level of the esophagus has a distinct but overlapping sensory projection to the spinal cord, and afferents from all parts of the esophagus overlap the known spinal distribution of cardiac afferents.     

Bradykinin as a pain mediator: receptors are localized to sensory neurons, and antagonists have analgesic actions.

Autoradiographic studies localize [3H]bradykinin receptor binding sites to the substantia gelatinosa, dorsal root, and a subset of small cells in both the dorsal root and trigeminal ganglia of the guinea pig. [3H]Bradykinin labeling is also observed over myocardial/coronary visceral afferent fibers. The localization of [3H]bradykinin receptors to nociceptive pathways supports a role for bradykinin in pain mediation. Several bradykinin antagonists block bradykinin-induced acute vascular pain in the rat. The bradykinin antagonists also relieve bradykinin- and urate-induced hyperalgesia in the rat paw. These results indicate that bradykinin is a physiologic mediator of pain and that bradykinin antagonists have analgesic activity in both acute and chronic pain models.     

Gait changes in patients with knee osteoarthritis are replicated by experimental knee pain

Objective

Medial knee osteoarthritis (OA) is characterized by pain and associated with abnormal knee moments during walking. The relationship between knee OA pain and gait changes remains to be clarified, and a better understanding of this link could advance the treatment and prevention of disease progression. This study investigated changes in knee moments during walking following experimental knee pain in healthy volunteers, and whether these changes replicated the joint moments observed in medial knee OA patients.

Methods

In a crossover study, 34 healthy subjects were tested on 3 different days; gait analyses were conducted before, during, and after pain induced by hypertonic saline injections (0.75 ml) into the infrapatellar fat pad. Isotonic saline and sham injections were used as control conditions. Peak moments in frontal and sagittal planes were analyzed. The results were compared with data from 161 medial knee OA patients. The patients were divided into less severe OA and severe OA categories, which was based on radiographic disease severity of the medial compartment.

Results

Experimental knee pain led to reduced peak moments in the frontal and sagittal planes in the healthy subjects, which were similar to the patterns observed in less severe OA patients while walking at the same speed.

Conclusion

In healthy subjects, pain was associated with reductions in knee joint moments during walking in a manner similar to less severe knee OA patients. The experimental model may be used to study mechanically‐driven knee OA progression and preventive measures against abnormal joint loading in knee OA.     

Discordance between pain and radiographic severity in knee osteoarthritis: Findings from quantitative sensory testing of central sensitization

Objective

Radiographic measures of the pathologic changes of knee osteoarthritis (OA) have shown modest associations with clinical pain. We sought to evaluate possible differences in quantitative sensory testing (QST) results and psychosocial distress profiles between knee OA patients with discordant versus congruent clinical pain reports relative to radiographic severity measures.

Methods

A total of 113 participants (66.7% women; mean ± SD age 61.05 ± 8.93 years) with knee OA participated in the study. Radiographic evidence of joint pathology was graded according to the Kellgren/Lawrence scale. Central sensitization was indexed through quantitative sensory testing, including heat and pressure–pain thresholds, tonic suprathreshold pain (cold pressor test), and repeated phasic suprathreshold mechanical and thermal pain. Subgroups were constructed by dichotomizing clinical knee pain scores (median split) and knee OA grade scores (grades 1–2 versus 3–4), resulting in 4 groups: low pain/low knee OA grade (n = 24), high pain/high knee OA grade (n = 32), low pain/high knee OA grade (n = 27), and high pain/low knee OA grade (n = 30).

Results

Multivariate analyses revealed significantly heightened pain sensitivity in the high pain/low knee OA grade group, while the low pain/high knee OA grade group was less pain‐sensitive. Group differences remained significant after adjusting for differences on psychosocial measures, as well as age, sex, and race.

Conclusion

The results suggest that central sensitization in knee OA is especially apparent among patients with reports of high levels of clinical pain in the absence of moderate‐to‐severe radiographic evidence of pathologic changes of knee OA.

     

Spinal motor and sensory neurons are androgen targets in an acrobatic bird

Sex steroids affect the motivation to court mates, but less is known about how they influence motor movements associated with courtship behavior. Steroidal control of motor function may be especially important for species in which courtship requires superior strength, stamina, and neuromuscular coordination. Here we use the golden-collared manakin (Manacus vitellinus) to examine whether the neuromuscular circuitry that controls motoric aspects of courtship activity is sensitive to androgens. Males of this tropical species attract mates by rapidly jumping among branches in a courtship arena and using their wings to produce loud wing snaps. Testosterone activates this display via the androgen receptor (AR), and past work reveals that manakins injected with radio-labeled T ((3)H-T) accumulate radioactivity in the spinal cord. Thus, we used quantitative PCR to measure AR, estrogen receptor-α (ER-α) subtype, and aromatase (AROM) mRNA in spinal cords of male and female manakins and zebra finches. Expression of AR, but not ER-α or aromatase, was higher throughout the manakin spinal cord compared with the zebra finch. Next, we tested whether AR-expressing skeletal muscles are innervated by motor and sensory neurons that also express AR. To do this, we backfilled spinal neurons by injecting fluorescent tracers into select AR-sensitive wing and leg muscles of wild caught male and female manakins. We then removed these spinal cords and measured AR expression with in situ hybridization. Both sexes showed abundant AR mRNA in the cervical and lumbosacral spinal enlargements as well as in dorsal root ganglia attached to these enlargements. Together our findings suggest that androgens act widely on peripheral motor and sensory circuits in golden-collared manakins to influence wing snapping displays.     

广州管圆线虫病导致的脊神经根病4例

广州管圆线虫病是由广州管圆线虫所引起的人畜共患疾病，是人类嗜酸细胞性脑膜脑炎的主要原因之一。本病引起单纯的脊髓感觉神经根病，文献报道极为罕见。现报告４例如下。例１女，３８岁。因突发左上肢疼痛１３天于１９９７年１１月１９日入院。患者于１１月６日突然出现...