Dataset Information

Blockade of nerve sprouting and neuroma formation markedly attenuates the development of late stage cancer pain.

ABSTRACT: For many patients, pain is the first sign of cancer and, while pain can be present at any time, the frequency and intensity of pain tend to increase with advancing stages of the disease. Thus, between 75 and 90% of patients with metastatic or advanced-stage cancer will experience significant cancer-induced pain. One major unanswered question is why cancer pain increases and frequently becomes more difficult to fully control with disease progression. To gain insight into this question we used a mouse model of bone cancer pain to demonstrate that as tumor growth progresses within bone, tropomyosin receptor kinase A (TrkA)-expressing sensory and sympathetic nerve fibers undergo profuse sprouting and form neuroma-like structures. To address what is driving the pathological nerve reorganization we administered an antibody to nerve growth factor (anti-NGF). Early sustained administration of anti-NGF, whose cognate receptor is TrkA, blocks the pathological sprouting of sensory and sympathetic nerve fibers, the formation of neuroma-like structures, and inhibits the development of cancer pain. These results suggest that cancer cells and their associated stromal cells release nerve growth factor (NGF), which induces a pathological remodeling of sensory and sympathetic nerve fibers. This pathological remodeling of the peripheral nervous system then participates in driving cancer pain. Similar to therapies that target the cancer itself, the data presented here suggest that, the earlier therapies blocking this pathological nerve remodeling are initiated, the more effective the control of cancer pain.

SUBMITTER: Mantyh WG

PROVIDER: S-EPMC2992976 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Blockade of nerve sprouting and neuroma formation markedly attenuates the development of late stage cancer pain.

Mantyh W G WG Jimenez-Andrade J M JM Stake J I JI Bloom A P AP Kaczmarska M J MJ Taylor R N RN Freeman K T KT Ghilardi J R JR Kuskowski M A MA Mantyh P W PW

Neuroscience 20100920 2

For many patients, pain is the first sign of cancer and, while pain can be present at any time, the frequency and intensity of pain tend to increase with advancing stages of the disease. Thus, between 75 and 90% of patients with metastatic or advanced-stage cancer will experience significant cancer-induced pain. One major unanswered question is why cancer pain increases and frequently becomes more difficult to fully control with disease progression. To gain insight into this question we used a m ...[more]

PMID: 20851743

Similar Datasets

Project description:BackgroundThe appearance of dumbbell neuroma of the first thoracic root is extremely rare. The extradural component of a T1-dumbbell neuroma may present as an apical mass. The diagnosis of hand weakness is complex and may be delayed in T1-neuroma because of absence of the palpable cervical mass. One-stage removal of a T1-root neuroma and its intrathoracic extension demanded an extended posterior midline approach in the sitting position.Case presentationA 51-year old man had suffered a traumatic partial tendon rupture of his wrist flexor muscles 6 years ago. Since the incident he occasionally felt fullness and tenderness in the affected forearm with some tingling in his fingers bilaterally. During the last two years the hand weakness was continuous and hypotrophy of the medial flexor and intrinsic hand muscles had become apparent. Electrophysiological studies revealed an ulnar neuropathy in addition to mild median and radial nerve dysfunction, including a mild contralateral carpal tunnel syndrome. The diagnostic work-up for multiple mononeuropathy in the upper extremity was negative. Repeated electrophysiological studies revealed fibrillations in the C7 paravertebral muscles on the affected side. Chest x-ray revealed a large round apical mass on the affected side. A Horner's syndrome was noted at this point of diagnostic work-up. MRI of the cervical and thoracic spine revealed a dumbbell T1 neuroma enlarging the intervertebral foramen at T1-2 and a 5 cm large extradural tumor with extension into the apex of the ipsilateral lung. The patient underwent surgery in sitting position using a left dorsal midline approach. Although the T1 root could not be preserved, the patient's neurological condition was unchanged after the surgery.ConclusionExtended posterior midline exposure described here using hemilaminectomy, unilateral facetectomy and costo-transversectomy is efficient and safe for one-stage removal of dumbbell tumors at the T1 level with a predominantly extraforaminal component in the apex of the lung extending up to 6-7 cm laterally. Horner's syndrome, if present and observed, may significantly narrow the differential diagnosis of hand weakness caused by T1-root tumors.

Dataset Information

Blockade of nerve sprouting and neuroma formation markedly attenuates the development of late stage cancer pain.

Publications

Blockade of nerve sprouting and neuroma formation markedly attenuates the development of late stage cancer pain.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets