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Behavioral indices of ongoing pain are largely unchanged in male mice with tissue or nerve injury-induced mechanical hypersensitivity.

ABSTRACT: Despite the impact of chronic pain on the quality of life in patients, including changes to affective state and daily life activities, rodent preclinical models rarely address this aspect of chronic pain. To better understand the behavioral consequences of the tissue and nerve injuries typically used to model neuropathic and inflammatory pain in mice, we measured home cage and affective state behaviors in animals with spared nerve injury, chronic constriction injury (CCI), or intraplantar complete Freund's adjuvant. Mechanical hypersensitivity is prominent in each of these conditions and persists for many weeks. Home cage behavior was continuously monitored for 16 days in a system that measures locomotion, feeding, and drinking, and allows for precise analysis of circadian patterns. When monitored after injury, animals with spared nerve injury and complete Freund's adjuvant behaved no differently from controls in any aspect of daily life. Animals with CCI were initially less active, but the difference between CCI and controls disappeared by 2 weeks after injury. Further, in all pain models, there was no change in any measure of affective state. We conclude that in these standard models of persistent pain, despite the development of prolonged hypersensitivity, the mice do not have significantly altered "quality of life." As alteration in daily life activities is the feature that is so disrupted in patients with chronic pain, our results suggest that the models used here do not fully reflect the human conditions and point to a need for development of a murine chronic pain model in which lifestyle changes are manifest.

SUBMITTER: Urban R

PROVIDER: S-EPMC3079194 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature

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Behavioral indices of ongoing pain are largely unchanged in male mice with tissue or nerve injury-induced mechanical hypersensitivity.

Urban Rochelle R Scherrer Gregory G Goulding Evan H EH Tecott Laurence H LH Basbaum Allan I AI

Pain 20110121 5

Despite the impact of chronic pain on the quality of life in patients, including changes to affective state and daily life activities, rodent preclinical models rarely address this aspect of chronic pain. To better understand the behavioral consequences of the tissue and nerve injuries typically used to model neuropathic and inflammatory pain in mice, we measured home cage and affective state behaviors in animals with spared nerve injury, chronic constriction injury (CCI), or intraplantar comple ...[more]

PMID: 21256675

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Project description:Endometriosis is a common cause of pain including radicular pain. Ectopic endometrial tissue may directly affect peripheral nerves including the sciatic, which has not been modelled in animals.We developed a rat model for sciatic endometriosis by grafting a piece of autologous uterine tissue around the sciatic nerve. Control animals underwent a similar surgery but received a graft of pelvic fat tissue.The uterine grafts survived and developed fluid-filled cysts; the adjacent nerve showed signs of swelling and damage. Mechanical and cold hypersensitivity and allodynia of the ipsilateral hindpaw developed gradually over the first 2 weeks after the surgery, peaked at 2-5 weeks, and was almost resolved by 7 weeks. Control animals showed only minor changes in these pain behaviours. Histological signs of inflammation in the uterine graft and in the adjacent nerve were observed at 3 weeks but were resolving by 7 weeks. In vivo fibre recording showed increased spontaneous activity, especially of C-fibres, in sciatic nerve proximal to the uterine graft. Several pro-inflammatory cytokines including interluekin-18, VEGF, fractalkine, and MIP-1?, were elevated in the uterine graft plus sciatic nerve samples, compared to samples from normal nerve or nerve plus fat graft. Growth associated protein 43 (GAP43), a marker of regenerating nerve fibres, was observed in the adjacent sciatic nerve as well as in the uterine graft.This model shared many features with other rat models of endometriosis, but also had some unique features more closely related to neuropathic pain models.Some especially painful forms of endometriosis are essentially neuropathic, because peripheral nerves are directly affected by nearby ectopic endometrial tissue. We modelled endometriosis by implanting autologous uterine tissue around rat sciatic nerve. We observed mechanical and cold pain behaviours along with signs of inflammation and nerve damage and increased pro-inflammatory cytokines at the implant site. Pain behaviours correlated with signs of nerve inflammation and damage rather than with cyst survival.

Dataset Information

Behavioral indices of ongoing pain are largely unchanged in male mice with tissue or nerve injury-induced mechanical hypersensitivity.

Publications

Behavioral indices of ongoing pain are largely unchanged in male mice with tissue or nerve injury-induced mechanical hypersensitivity.

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