BackgroundThe exact mechanism of knee osteoarthritis (OA)-associated pain is unclear, whereas mixed evidence of inflammatory pain and neuropathic pain has been noted. We aimed to investigate pain-related sensory innervation in a monoiodoacetate (MIA)-induced model of OA.MethodsSixty of seventy female Sprague Dawley rats of six week-old underwent intra-articular MIA and fluorogold (FG) retrograde neurotracer injection into their right (ipsilateral) knee, while their left knees were treated with FG in saline as a control (contralateral knee). Other rats were treated with FG only bilaterally, and used as controls. Rats were evaluated for tactile allodynia using von Frey hairs. Proinflammatory mediators in the knee soft tissues, including tumor necrosis factor (TNF)-α, interleukin (IL)-6, and nerve growth factor (NGF), were quantified using ELISAs to evaluate inflammation in the knee after 1, 4, 7,14,21, and 28 days post injection:. Dorsal root ganglia (DRG) were immunostained for three molecules after 7,14,21, and 28 days post injection: calcitonin gene-related peptide (CGRP), a marker of inflammatory pain; and activating transcription factor-3 (ATF3) and growth associated protein-43 (GAP43), as markers for nerve injury and regenerating axons. The distribution of microglia in the spinal cord were also evaluated, because they have been reported to increase in neuropathic pain states. These evaluations were performed up to 28 days postinjection. P < 0.05 was considered significant.ResultsProgressive tactile allodynia and elevated cytokine concentrations were observed in ipsilateral knees. CGRP-immunoreactive (-ir) ipsilateral DRG neurons significantly increased, peaking at 14 days postinjection, while expression of FG-labeled ATF3-ir or ATF3-ir GAP43-ir DRG neurons significantly increased in a time-dependent manner. Significant proliferation of microglia were found with time in the ipsilateral dorsal horn.ConclusionsPain-related characteristics in a MIA-induced rat OA model can originate from an inflammatory pain state induced by the local inflammation initiated by inflammatory cytokines, and that state will be followed by gradual initiation of neuronal injury, which may induce the neuropathic pain state.
PurposePain from osteoarthritis (OA) is generally classified as nociceptive (inflammatory). Animal models of knee OA have shown that sensory nerve fibers innervating the knee are significantly damaged with destruction of subchondral bone junction, and induce neuropathic pain (NP). Our objective was to examine NP in the knees of OA patients using painDETECT (an NP questionnaire) and to evaluate the relationship between NP, pain intensity, and stage of OA.Materials and MethodsNinety-two knee OA patients were evaluated in this study. Pain scores using Visual Analogue Scales (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), painDETECT, duration of symptoms, severity of OA using the Kellgren-Lawrence (KL) system, and amount of joint fluid were evaluated and compared using a Spearman's correlation coefficient by rank test.ResultsOur study identified at least 5.4% of our knee OA patients as likely to have NP and 15.2% as possibly having NP. The painDETECT score was significantly correlated with the VAS and WOMAC pain severity. Compared with the painDETECT score, there was a tendency for positive correlation with the KL grade, and tendency for negative correlation with the existence and amount of joint fluid, but these correlations were not significant.ConclusionPainDETECT scores classified 5.4% of pain from knee OA as NP. NP tended to be seen in patients with less joint fluid and increased KL grade, both of which corresponded to late stages of OA. It is important to consider the existence of NP in the treatment of knee OA pain.
Significant improvements in disk height and spinal canal area were found after surgery. Bulging of disks was reduced through correction, and stretching the yellow ligament may have decompressed the spinal canal. Lumbar anterolateral fusion without laminectomy may be useful for lumbar spondylolisthesis with back and leg symptoms.
Our results demonstrate, for the first time, that human AF and NP cells constitutively express NGF protein and mRNA, and that the proinflammatory cytokines IL-1beta and TNF-alpha stimulate the production of NGF. The precise role of NGF produced by IVD cells in the generation of discogenic pain or on the metabolism of IVD cells, especially under certain physiologic conditions in which cytokines are up-regulated, needs to be clarified in future experimentation.
BackgroundThe importance of pelvic incidence-lumbar lordosis (PI-LL: PI minus LL) mismatch is emphasized in long-segment fusion for adult spinal deformity; however, there are few studies evaluating the influence of PI-LL on surgical outcomes after short-segment fusion. In this study, we have examined the effects of PI-LL mismatch on surgical outcomes of short-segment lumbar intervertebral fusion for lumbar degenerative diseases.MethodsPatients with lumbar degenerative disease treated by short-segment (1 or 2 levels) transforaminal lumbar interbody fusion were divided into Group A (PI-LL ≤ 10°: n = 22) and Group B (PI-LL ≥ 11°: n = 30). Pre-and post-operative patient symptoms were assessed by the visual analogue scale (VAS: scores 0-100 mm; for LBP, lower-extremity pain, and lower-extremity numbness), a detailed VAS for LBP while in motion, standing, and sitting, and the Oswestry disability index (ODI). Surgical outcomes were evaluated by the Nakai score (3 = excellent to 0 = poor. Post-operative data were acquired for at least one year following surgery and were compared between the two groups. Multiple regression analyses were used to evaluate the relative influence of PI-LL on each pre-and post-operative parameter (VAS, detailed VAS and ODI) adjusted for age, sex, fusion levels, body mass index, presence of scoliosis, diabetes mellitus and depression.ResultsThe surgical outcomes in Group A were significantly better than those of Group B. Group A showed better post-operative VAS scores for LBP, particularly LBP while standing (11.9 vs. 25.8). The results of the multivariate analyses showed no significant correlation between PI-LL and pre-operative symptoms, but did show a significant correlation between PI-LL and the post-operative VAS score for LBP, lower extremity pain, and numbness.ConclusionsThis study is the first to find that PI-LL mismatch influences post-operative residual symptoms, such as LBP, lower extremity pain and numbness. Among the three types of LBP examined in the detailed VAS, LBP while standing was most strongly related to PI-LL mismatch. The importance of maintaining spinopelvic alignment is emphasized, particularly when treating patients with adult spinal deformity using long-segment fusion surgery. However, our results indicate that surgeons should pay attention to sagittal spinopelvic alignment and avoid post-operative PI-LL mismatch even when treating patients with short-segment lumbar interbody fusion.
Daily subcutaneous injection of teriparatide for bone union using local bone grafting after instrumented lumbar posterolateral fusion in women with postmenopausal osteoporosis was more effective than oral administration of bisphosphonate.
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