Functional role of exogenous administration of substance P in chronic constriction injury model of neuropathic pain in gerbils

Meert, Theo; Vissers, Kris; Geenen, Frank; Kontinen, Vesa K.

doi:10.1016/s0091-3057(03)00187-4

Cited by 30 publications

(11 citation statements)

References 54 publications

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“…SP is released from axon terminals upon C-fiber stimulation (Malcangio et al, 2000), and its expression in the superficial laminae of the spinal cord decreases after lumbar neural injuries (Munglani et al, 1996;Malmberg and Basbaum, 1998;Allen et al, 1999). CGRP affects nociception by promoting the release, and slowing the metabolism, of SP (Allen et al, 1999;Meert et al, 2003). Allodynia increases following intrathecal CGRP administration and decreases after administration of a CGRP antagonist (Oku et al, 1987;Cridland and Henry, 1989;Bennett et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Transient cervical nerve root compression modulates pain: Load thresholds for allodynia and sustained changes in spinal neuropeptide expression

Hubbard¹,

Chen²,

Winkelstein³

2008

Journal of Biomechanics

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Nerve root compression produces chronic pain and altered spinal neuropeptide expression. This study utilized controlled transient loading in a rat model of painful cervical nerve root compression to investigate the dependence of mechanical allodynia on load magnitude. Injury loads (0-110mN) were applied quasistatically using a customized loading device, and load thresholds to produce maintained mechanical allodynia were defined. Bilateral spinal expression of substance P (SP) and calcitonin gene-related peptide (CGRP) was assessed 7 days following compression using immunohistochemistry to determine relationships between these neuropeptides and compression load. A three-segment change point model was implemented to model allodynia responses and their relationship to load. Load thresholds were defined at which ipsilateral and contralateral allodynia were produced and sustained. The threshold for increased allodynia was lowest for acute (day 1) ipsilateral responses (26.29mN), while thresholds for allodynia on day 7 were similar for the ipsilateral (38.16mN) and contralateral forepaw (38.26mN). CGRP, but not SP, significantly decreased with load; the thresholds for ipsilateral and contralateral CGRP decreases corresponded to 19.52mN and 24.03mN, respectively. These thresholds suggest bilateral allodynia may be mediated by spinal mechanisms, and that these mechanisms depend on the magnitude of load.

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Section: Introductionmentioning

confidence: 99%

Transient cervical nerve root compression modulates pain: Load thresholds for allodynia and sustained changes in spinal neuropeptide expression

Hubbard¹,

Chen²,

Winkelstein³

2008

Journal of Biomechanics

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“…Data suggest that SP acting at NK1 receptors underlies heightened pain states resulting from inflammatory 1,13,14,17,29,30,32,37,39 and neuropathic 1,7,14,18,24,27,29,33,35,38,41,44 pain conditions, as well as experimentally-induced states of central sensitization. 2,19,45 However, less is known regarding the role of SP and its receptor in morphine analgesic tolerance, a condition that has been characterized by an increased sensitivity to pain.…”

Section: Discussionmentioning

confidence: 99%

“…8 Since SP is synthesized by small diameter primary afferent fibers 6 and its receptor, the neurokinin 1 (NK1) receptor, is densely distributed in spinal cord lamina I nociceptive-specific neurons, 1 both SP and its receptors are well situated to send and receive nociceptive input from the periphery. Indeed, both have been implicated in the heightened nociception that accompanies inflammatory, 1,13,14,17,29,30,32,37,39 neuropathic, 1,7,14,18,24,27,29,33,35,38,41,44 and experimentally-induced states of central sensitization (eg, capsaicin or mustard oil application, repeated afferent stimulation). 2,19,45 There is evidence to suggest that SP-NK1 neurotransmission is also involved in morphine tolerance.…”

mentioning

confidence: 99%

Decreased Substance P and NK1 Receptor Immunoreactivity and Function in the Spinal Cord Dorsal Horn of Morphine-Treated Neonatal Rats

Thomson

Terman

Zeng

et al. 2008

The Journal of Pain

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“…After checking for haemostasis, the muscle, the adjacent fascia and the skin were closed with sutures. For the validation of this technique in gerbils we refer to the article of Meert et al 14 …”

Section: Methodsmentioning

confidence: 99%

Is the Second Phase of the Formalin Test Useful to Predict Activity in Chronic Constriction Injury Models? A Pharmacological Comparison in Different Species

et al. 2003

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This study presents data of several reference drugs in rats and gerbils for both the second phase of the formalin test and the cold allodynia in animals with a constriction injury of the sciatic nerve. A pharmacological validation of the formalin test and the CCI model in gerbils was performed. It was evaluated whether the second phase of the formalin test could be used as a pharmacological screening to predict outcome in the cold plate test in CCI animals. Male Sprague Dawley and Wistar rats and male gerbils were used for both tests. For the formalin test, animals were injected in the right hind paw (5% formalin rat: 0.05 microl; gerbil: 0.01 microl) and flinching and licking or biting were recorded. For CCI testing, a Bennett operation was performed on the left hind paw 7 days before testing. Cold plate allodynia was evaluated before and after drug treatment. In rats, a good correlation between both test conditions for morphine, fentanyl, MK-801 and flunarizine was found. Clonidine tends to have more activity in the second phase of the formalin test, whereas baclofen, tramadol, amitryptiline, ketamine and topiramate demonstrate to be more active in the cold plate. In gerbils, a good correlation between both test conditions for fentanyl and ketoprofen was found. Tramadol and CP-96345 tend to have more activity in the second phase of the formalin test, whereas morphine, SR-48968, SR-142801 and R116301 demonstrates to be more active in the cold plate test. In the present acute test conditions, there is a correlation in the pharmacological activity in rats and gerbils for the tested compounds a correlation between the second phase of the formalin test and the cold allodynia in CCI animals is found. Comparing to human data the screening drugs tested in this study show a correlation between animal and human studies in these specific circumstances. Further validation studies are needed to make these correlations clinical applicable.

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Functional role of exogenous administration of substance P in chronic constriction injury model of neuropathic pain in gerbils

Cited by 30 publications

References 54 publications

Transient cervical nerve root compression modulates pain: Load thresholds for allodynia and sustained changes in spinal neuropeptide expression

Transient cervical nerve root compression modulates pain: Load thresholds for allodynia and sustained changes in spinal neuropeptide expression

Decreased Substance P and NK1 Receptor Immunoreactivity and Function in the Spinal Cord Dorsal Horn of Morphine-Treated Neonatal Rats

Is the Second Phase of the Formalin Test Useful to Predict Activity in Chronic Constriction Injury Models? A Pharmacological Comparison in Different Species

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