Name: Urokinase-type Plasminogen Activator-induced Mouse Back Pain Model (Video) | JoVE Journal
Uploaded: 2023-09-01T12:00:00.000+00:00
Duration: 6 min 20 s
Description: Learn a non-invasive method to induce chronic back pain in mice using urokinase-type plasminogen activator intraligament injection. This reliable technique requires minimal training and supports pain mechanism research for up to ten weeks.

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Grant funding was provided by NIH HEAL UG3 NS123958. The housing facilities were inspected and accredited by AAALAC. Animals were housed in the Animal Resources Center (ARC) housing facility maintained by the laboratory staff and Division of Laboratory and Animal Resources (DLAR) staff. The procedures for behavioral testing are standard methods in the field as approved by the American Pain Society and the International Association for the Study of Pain. The method of euthanasia is consistent with recommendations of the Panel on Euthanasia of the American Veterinary Medical Association.

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The authors declare no competing financial interests. KNW acknowledges unpaid consultation with NeuroChronix, Bessor Pharma, and USA Elixeria BioPharm, Inc.

This model of chronic back pain is simple to induce, and hypersensitivity established within 1 week can last for up to (and possibly beyond) 8 weeks. This allows for accurate study of the chronic pain state as opposed to other acute models that only last for a week or two. While we show the model in mice, the uPA-induced CBP model can also be established in rats2. An advantage of the model is that the prolonged time course provokes the development of anxiety- and depression-like behaviors, which a...

Low back pain is one of the most common causes of disability with 1 in 5 people suffering worldwide1. In spite of these efforts, few reliable animal models of back pain are popularly used in animal research in the pain field, especially in mice. Previous models have almost exclusively made use of rats for the induction of chronic back pain (CBP) such as those induced by injection of urinary plasminogen activator (uPA) into the lumbar facet joint2,3, injection of nerve growth factor (NGF) into trunk musculature4, or monosodium iodoacetate (MIA)5 or interleukin-1beta6 injection in the intravertebral disc. Of course, rats are preferred for these models mainly due to their larger size and ease of access for injection of inflammatory agents.
To be clear, mouse models of back pain do exist such as the SPARC-null mouse model of intervertebral-disc degeneration used for many years7, but these are more costly and time-consuming to establish than injection-based models. A recent mouse study established a model of lower back pain by combining NGF injection into low back muscles with vertical chronic restraint stress8. In the following protocol, we have adapted the uPA-induced CBP model from rats for mice2. Hypersensitivity is established within 1 week and persists up to 6-8 weeks. In addition, we establish that mice develop anxiety- and depression-like behaviors. Given the prevalence of back pain and the more common use of mice in molecular pain research, this durable model is readily established for use in the development of new treatment strategies for back pain relief.

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urokinase-type plasminogen activator-induced mouse back pain model

Urokinase-type Plasminogen Activator-induced Mouse Back Pain Model

A model of persisting lower back pain can be induced in mice with the simple methodology described herein. Step-by-step methods for simple, rapid induction of a persisting back pain model in mice are provided here using an injection of urokinase-type plasminogen activator (urokinase), a serine protease present in humans and other animals. The methodology for induction of persisting lower back pain in mice involves a simple injection of urokinase along the ligamentous insertion region of the lumbar spine. The urokinase inflammatory agent activates plasminogen to plasmin. Typically, the model can be induced within 10 min and hypersensitivity persists for at least 8 weeks.
Hypersensitivity, gait disturbance, and other standard anxiety- and depression-like measures can be tested in the persisting model.&#160;Back pain is the most prevalent type of pain. To improve awareness of back pain, the International Association for the Study of Pain (IASP) named 2021 the &#34;Global Year about Back Pain&#34; and 2022 the &#34;Global Year for Translating Pain Knowledge to Practice.&#34; One limitation of the therapeutic advancement of pain therapeutics is the lack of suitable models for testing persistent and chronic pain. The&#160;features of this model&#160;are suitable for testing potential therapeutics aimed at the reduction of back pain and its ancillary characteristics, contributing to IASP&#39;s naming 2022 as the Global Year for Translating Pain Knowledge to Practice.

Nociceptive-related behavioral testing and data analysis 
Evoked measures 
Hypersensitivity on the footpad develops within a day of urokinase injection. Within 1 week, the withdrawal threshold is significantly decreased and persists until euthanasia; this is shown through postsurgical week 4 (Figure 4A). Paw withdrawal latency is analyzed using the von Frey up-down method9 and the Hargreaves test. In the example plotted, mice wi...

Methods for simple, rapid induction of a back pain model in mice are provided here using an intraligament injection of urinary plasminogen activator.

A model of persisting lower back pain can be induced in mice with the simple methodology described herein. Step-by-step methods for simple, rapid ...

urokinase-type-plasminogen-activator-induced-mouse-back-pain-model

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Learn a non-invasive method to induce chronic back pain in mice using urokinase-type plasminogen activator intraligament injection. This reliable technique requires minimal training and supports pain mechanism research for up to ten weeks.

Urokinase-type Plasminogen Activator-induced Mouse Back Pain Model

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