Severity of intervertebral disc herniation regulates cytokine and chemokine levels in patients with chronic radicular back pain.

OBJECTIVE: The contributions of intervertebral disc disease and subject-specific covariates to systemic inflammation in low back pain are unknown. We examined the effects of symptomatic disc herniation (DH) and MRI herniation severity on serum cytokine levels in clinical subjects. DESIGN: Cytokine levels from lumbar DH subjects (N = 78) were compared to control subjects (N = 57) accounting for effects of DH, age, body mass index (BMI) and gender. Effect of DH severity on cytokine levels was analyzed on subsets of subjects with acute or chronic pain. Serum cytokines were also analyzed in a subset of patients between pre- and 3 months post-surgery. RESULTS: Cytokine levels were elevated in the serum of patients with symptomatic DH, and the covariates age, BMI and gender significantly contributed to levels of some cytokines. Severity of herniation was a significant contributor to pain intensity (VAS), serum levels of HMGB1, PDGFbb, and IL-9. The relationship between DH severity and cytokine levels was confirmed in subjects with chronic, but not acute symptoms. Serum levels of macrophage migration inhibitory factor (MIF) decreased, whereas levels of CCL3, CCL11, CXCL1, and CXCL10 were significantly elevated post surgery. CONCLUSIONS: This study is the first to show that DH severity is coordinately associated with changes in serum levels of inflammatory cytokines in chronic pain subjects. HMGB1, PDGFbb and IL-9 are novel mediators of increasing DH severity, indicative of cellular damage, neuro-inflammation and angiogenesis. Resolution of inflammation was observed with decrease in MIF post surgery. However, elevated chemokine levels indicate ongoing remodeling and wound healing at 3-month time point.

Intravesical Escherichia coli lipopolysaccharide stimulates an increase in bladder nerve growth factor.

OBJECTIVE: To investigate the effects of the intravesical instillation of Escherichia coli lipopolysaccharide (LPS) on nerve growth factor (NGF, which may mediate the pain associated with inflammation) protein and mRNA in the bladders of mice. MATERIALS AND METHODS: E. coli LPS was instilled into the bladders of female mice; the whole-bladder NGF content was then determined by an enzyme-linked immunosorbent assay and the NGF mRNA content of the bladder determined by semiquantitative reverse transcription-polymerase chain reaction. Bladder NGF was also evaluated by immunohistochemistry in some of the mice. RESULTS: LPS stimulated a significant increase in bladder NGF 90 min after instillation, but bladder NGF content was significantly less than that in bladders of control mice 3 and 7 h after LPS instillation. Twenty-four hours after the intravesical infusion of saline or LPS, there was no difference in NGF content in bladders from saline or LPS-infused mice. Immunohistochemistry confirmed the presence of increased NGF in the mucosa of detrusor from bladders 90 min after LPS instillation. Bladder NGF mRNA increased more slowly in response to LPS, and 7 and 24 h after LPS instillation the relative abundance of NGF mRNA was 1.5 and 2.0 times greater in LPS-infused bladders, respectively. CONCLUSIONS: E. coli LPS can stimulate increased NGF message and protein in the bladder. The increase in NGF protein preceded the increase in mRNA, suggesting that this increase was not the result of gene transcription. It is possible that NGF participates in the pathogenesis of pain associated with bacterial cystitis.

Pancreatic spasmolytic polypeptide (PSP): I. Preparation and initial chemical characterization of a new polypeptide from porcine pancreas.

A novel polypeptide, named Pancreatic Spasmolytic Polypeptide (PSP), was discovered in a side-fraction from the purification of porcine insulin. PSP was prepared by two different purification methods based on combinations of precipitations, anion-exchange and cation-exchange chromatography. The highest yield obtained, 52 mg PSP/kg pancreas, indicates that the content of PSP in porcine pancreas is about half the content of insulin. Both preparations appeared to be very pure as judged by basic disc electrophoresis, isoelectric focusing, analytical gel filtration and radioimmunoassays for various polypeptides known to be present in pancreas. The PSP molecule contains 106 amino acids (MW about 11 700). PSP is an acidic (pI 4.4), non-glycosylated protein without free N-terminal amino groups, and with high contents of proline and cystine. The high content of S-S bridges (7 per molecule), an unexpected low apparent MW determined by gel filtration, and a remarkable resistance towards treatment with trypsin and chymotrypsin, point to a compact structure of the PSP molecule.