Hyperalgesia due to nerve injury: role of neutrophils

Perkins, N. M; Tracey, David J.

doi:10.1016/s0306-4522(00)00396-1

Cited by 194 publications

(128 citation statements)

References 75 publications

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“…23,37,43 One can imagine that fractalkine might be inducing neural inflammatory cell infiltration in CP after its release from intrapancreatic nerves, and thus be a key mediator of pancreatic neuritis. The participation of a chemokine as the mediator in this process is supported by the fact that increasing inflammatory cell infiltration around sympathetic nerve fibers is in part triggered by cytokine and chemokine release by macrophages.…”

Section: Discussionmentioning

confidence: 99%

Neural fractalkine expression is closely linked to pain and pancreatic neuritis in human chronic pancreatitis

Ceyhan

Deucker

Demir

et al. 2009

Laboratory Investigation

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The chemokine fractalkine induces migration of inflammatory cells into inflamed tissues, thereby aggravating inflammatory tissue damage and fibrosis. Furthermore, fractalkine increases neuropathic pain through glial activation, which can be diminished by blocking of its receptor, CX3CR1, through neutralizing antibodies. As chronic pancreatitis (CP) is characterized by tissue infiltration of inflammatory cells, fibrosis, pancreatic neuritis and severe pain, the roles of fractalkine and CX3CR1 were investigated in CP (n ¼ 61) and normal pancreas (NP, n ¼ 21) by QRT-PCR, western blot and immunohistochemistry analyses. Their expression correlated with the severity of pancreatic neuritis, fibrosis, intrapancreatic nerve fiber density and hypertrophy, pain, CP duration and with the amount of inflammatory cell infiltrate immuno-positive for CD45 and CD68. To investigate the influence of fractalkine on pancreatic fibrogenesis, human pancreatic stellate cells (hPSCs) were isolated from patients with CP, incubated with fractalkine and then Collagen-1 and a-smooth muscle actin (a-SMA) expressions were measured. CX3CR1, but not fractalkine, mRNA was overexpressed in CP. In contrast, the protein levels of both CX3CR1 and fractalkine were upregulated. Neuro-immunoreactivity for fractalkine and CX3CR1 was strongest in patients suffering from severe pain and pancreatic neuritis. Long-term suffering from CP was noticeably related to increased neural immunoreactivity of fractalkine. Furthermore, fractalkine and CX3CR1 mRNA overexpressions were associated with enhanced lymphocyte and macrophage infiltration. Advanced fibrosis was associated with increased fractalkine expression, whereas in vitro fractalkine had no significant impact on collagen-1 and a-SMA expressions in hPSCs. Therefore, pancreatic fractalkine expression appears to be linked to visceral pain and to the recruitment of inflammatory cells into the pancreatic tissue and nerve fibers, with subsequent pancreatic neuritis. However, pancreatic fibrogenesis is probably indirectly influenced by fractalkine. Taken together, these novel findings suggest that CX3CR1 represents a potential novel therapeutic target to reduce inflammation and modulate pain in CP.

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Section: Discussionmentioning

confidence: 99%

Neural fractalkine expression is closely linked to pain and pancreatic neuritis in human chronic pancreatitis

Ceyhan

Deucker

Demir

et al. 2009

Laboratory Investigation

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“…Although immune responses are associated with both CCI and PSL (see section II.C.5.a), peripheral opioid antinociception was commonly observed after CCI but not after PSL. It is noteworthy that immune cells accumulate directly at the nerve lesion (i.e., at the nerve trunk) but usually not in peripheral tissues (e.g., paws) innervated by the damaged neurons (Perkins and Tracey, 2000;). However, a large number of studies reported antinociception after opioid injection into paws.…”

Section: Neuropathic Pain a Immune Response And Pain After Nerve Dammentioning

confidence: 99%

Modulation of Peripheral Sensory Neurons by the Immune System: Implications for Pain Therapy

2011

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“…Since monocyte and macrophage heterogeneity may be complex (for review, see Gordon and Taylor, 2005), it is currently unknown whether a specific subset of monocytes/macrophages are responsible for these effects. In addition to monocytes and macrophages, both neutrophils and T lymphocytes have been shown to influence pain sensitivity after nerve trauma (Perkins and Tracey, 2000;Moalem et al, 2004). However, whether blocking the entry of specific immune cell subsets will provide an adequate treatment of pain after injury will have to be reevaluated by taking into consideration other key responses such as axonal regeneration, nerve repair, and functional recovery.…”

Section: Introductionmentioning

confidence: 99%

Functional Recovery after Peripheral Nerve Injury is Dependent on the Pro-Inflammatory Cytokines IL-1β and TNF: Implications for Neuropathic Pain

Nadeau¹,

Filali²,

Zhang³

et al. 2011

J. Neurosci.

301

226

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IL-1␤ and TNF are potential targets in the management of neuropathic pain after injury. However, the importance of the IL-1 and TNF systems for peripheral nerve regeneration and the mechanisms by which these cytokines mediate effects are to be fully elucidated. Here, we demonstrate that mRNA and protein levels of IL-1␤ and TNF are rapidly upregulated in the injured mouse sciatic nerve. Mice lacking both IL-1␤ and TNF, or both IL-1 type 1 receptor (IL-1R1) and TNF type 1 receptor (TNFR1), showed reduced nociceptive sensitivity (mechanical allodynia) compared with wild-type littermates after injury. Microinjecting recombinant IL-1␤ or TNF at the site of sciatic nerve injury in IL-1␤-and TNF-knock-out mice restored mechanical pain thresholds back to levels observed in injured wild-type mice. Importantly, recovery of sciatic nerve function was impaired in IL-1␤-, TNF-, and IL-1␤/TNF-knock-out mice. Notably, the infiltration of neutrophils was almost completely prevented in the sciatic nerve distal stump of mice lacking both IL-1R1 and TNFR1. Systemic treatment of mice with an anti-Ly6G antibody to deplete neutrophils, cells that play an essential role in the genesis of neuropathic pain, did not affect recovery of neurological function and peripheral axon regeneration. Together, these results suggest that targeting specific IL-1␤/ TNF-dependent responses, such as neutrophil infiltration, is a better therapeutic strategy for treatment of neuropathic pain after peripheral nerve injury than complete blockage of cytokine production.

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Hyperalgesia due to nerve injury: role of neutrophils

Cited by 194 publications

References 75 publications

Neural fractalkine expression is closely linked to pain and pancreatic neuritis in human chronic pancreatitis

Neural fractalkine expression is closely linked to pain and pancreatic neuritis in human chronic pancreatitis

Modulation of Peripheral Sensory Neurons by the Immune System: Implications for Pain Therapy

Functional Recovery after Peripheral Nerve Injury is Dependent on the Pro-Inflammatory Cytokines IL-1β and TNF: Implications for Neuropathic Pain

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