- Email: [email protected]
(114) Anatomical and behavioral correlates of the bilateral chronic constriction injury of neuropathic pain in rats
P4
Abstracts
(112) Acute neck trauma in rats produces diffuse and chronic changes in nociceptive responding
(114) Anatomical and behavioral correlates of the bilateral chronic constriction injury of neuropathic pain in rats
S Harte, J Meyers, D Clauw, T Morrow; University of Michigan, Ann Arbor, MI Acute musculoskeletal injuries sometimes lead to chronic regional or widespread pain, as well as diffuse hyperalgesia/allodynia. Animal models of post-traumatic pain would be useful to study the neurobiology of this phenomenon. In one such model, unilateral injections of acidic saline into the rodent hindlimb produce bilateral, mechanical hyperalgesia in the hindpaws that persists for approximately 30 days (Sluka et al., Muscle & Nerve, 2001). However, human studies suggest that proximal musculoskeletal trauma is more closely linked to chronic pain than distal trauma. Also, the contralateral limb to an initial injury could develop nociceptive changes because of segmental rather than central mechanisms. Therefore, we modified this model and injected acidic saline into the neck, and measured the subsequent nociceptive response in the hindpaws, as a measure of the “extra-segmental” response to this initial injury. Male, Sprague-Dawley rats were injected with 200 l of sterile acidic saline (pH 4.0) on Days 0 and 5 into the deep muscles of the neck. Nociceptive responses were measured by evaluating withdrawal responses in both hindpaws to mechanical cutaneous stimulation. Preliminary results showed that neck injections of acidic saline produced mechanical hyper-responsiveness in both hindpaws. In contrast to the pain produced by acid injections into the hindlimb, the development of mechanical hyper-responsiveness following neck injections was delayed for 19-26 days after the first acid injection and it persisted for more than 60 days. Histological analysis of postmortem neck tissue revealed no persistent inflammatory response or muscle pathology in the area of acid injection. Control rats that underwent identical injections with physiologically neutral saline had no changes in nociceptive responding. These preliminary findings suggest that trauma to the neck can lead to chronic and diffuse changes in nociceptive processing, even after the acute injury has healed, as has been noted in conditions such as fibromyalgia.
S Datta, K Chattejee, R Kline, R Wiley; Tennessee Valley Healthcare System, Nashville, TN Society for Neuroscience abstract
(113) Pregabalin attenuates mechanical and cold allodynia in Zucker diabetic fatty rats
(115) Involvement of sex hormones in a mice model of neuropathic pain
S Dima, M Urban, E Crown; Merck, West Point, PA Painful diabetic neuropathy is the most common known cause of neuropathy worldwide. Its prevalence is increasing rapidly as the rate of obesity rises in industrialized countries. This study used the Zucker diabetic fatty (ZDF) rat, a commonly used rat model of Type 2 diabetes, to evaluate the development of thermal and mechanical hypersensitivity and the effect of pregabalin on established painful neuropathy. Beginning at 9-weeks of age ZDF rats developed significant hyperglycemia compared to Zucker lean (ZL) controls (ZDF 369.5 ⫹/- 10.8 mg/dl, ZL 95.2 ⫹/- 1.3 mg/dl). Weekly behavioral testing showed no difference between groups for mechanical hyperalgesia (paw pinch test ZDF 200.8 ⫹/11.7 g, ZL 166.0 ⫹/- 4.5 g, 12 weeks of age) but ZDF rats had significantly lower withdrawal thresholds when measured for mechanical allodynia (von Frey test ZDF 5.8 ⫹/- 1.3 g, ZL 13.8 ⫹/- 0.8 g, 12 weeks of age p⬍0.001). Response latencies in ZDF rats were shorter compared to ZL rats for both hot (50¢aC hot plate ZDF 23.6 ⫹/- 2.6 s, ZL 40.2 ⫹/- 1.7 s at 11 weeks, p⬍0.05) and cold (5¢aC cold plate ZDF 25.1 ⫹/- 1.9 s, ZL 49.0 ⫹/4.7 s at 11 weeks, p⬍0.05) stimuli. Pregabalin (20 mg/kg PO) partially reversed the hypersensitivity to both mechanical and cold allodynia in ZDF rats (von Frey ZDF 4.4 ⫹/- 1.8 g pre-dose to 10.3 ⫹/- 0.8 g post-dose, p⬍0.05 and cold plate ZDF 28.9 ⫹/- 4.5 s pre-dose to 42.6 ⫹/- 4.3 s post-dose, p⬍0.05, 16 weeks of age) with no changes observed after pregabalin administration in ZL rats. These results demonstrate that ZDF rats develop symptoms of mechanical and cold allodynia that are attenuated by pregabalin administration.
P Robichaud, M Spooner, J Carrier, S Marchand; Universite´ de Sherbrooke, Sherbrooke, QC Differences between males and females in different types of pain are well-established. In a previous study, we demonstrated that sex hormones are responsible for excitatory and inhibitory mechanisms during the formalin test.1 However, the role of sex hormones in neuropathic pain remains elusive. In the present study, a peripheral nerve injury model (chronic constriction injury; CCI) was use to investigate gender differences in neuropathic pain using intact and gonadectomized mice of both sexes. Mice have been tested for mechanical allodynia (von Frey test) and thermal hyperalgesia (Hargreaves test) for up to 30 days (including 28 days post-CCI). Since we previously demonstrated that endogenous pain inhibitory mechanisms differ between sexes, a stress induced analgesia test (swim test) was also performed on our groups. Since glial cells are known to be involved in the development of neuropathic pain, a spinal marker of glial cells (GFAP) was studied to complement behavioural results. Animals with CCI presented more pain and a higher density of glial cells than controls. In accordance with our previous results with the formalin test, females have a lower pain threshold than males in both allodynia and hyperalgesia. Furthermore, castrated males have more pain and for a longer period of time than intact males, suggesting that testosterone plays a protective role in pain. Finally, pain inhibitory mechanisms seem to be recruited more efficiently in intact animals than in gonadectomized animals. These results show that sex hormones play an important role in the gender difference observed in neuropathic pain. (1. Gaumond, Brain Res, 2005.)
Abstracts
(112) Acute neck trauma in rats produces diffuse and chronic changes in nociceptive responding
(114) Anatomical and behavioral correlates of the bilateral chronic constriction injury of neuropathic pain in rats
S Harte, J Meyers, D Clauw, T Morrow; University of Michigan, Ann Arbor, MI Acute musculoskeletal injuries sometimes lead to chronic regional or widespread pain, as well as diffuse hyperalgesia/allodynia. Animal models of post-traumatic pain would be useful to study the neurobiology of this phenomenon. In one such model, unilateral injections of acidic saline into the rodent hindlimb produce bilateral, mechanical hyperalgesia in the hindpaws that persists for approximately 30 days (Sluka et al., Muscle & Nerve, 2001). However, human studies suggest that proximal musculoskeletal trauma is more closely linked to chronic pain than distal trauma. Also, the contralateral limb to an initial injury could develop nociceptive changes because of segmental rather than central mechanisms. Therefore, we modified this model and injected acidic saline into the neck, and measured the subsequent nociceptive response in the hindpaws, as a measure of the “extra-segmental” response to this initial injury. Male, Sprague-Dawley rats were injected with 200 l of sterile acidic saline (pH 4.0) on Days 0 and 5 into the deep muscles of the neck. Nociceptive responses were measured by evaluating withdrawal responses in both hindpaws to mechanical cutaneous stimulation. Preliminary results showed that neck injections of acidic saline produced mechanical hyper-responsiveness in both hindpaws. In contrast to the pain produced by acid injections into the hindlimb, the development of mechanical hyper-responsiveness following neck injections was delayed for 19-26 days after the first acid injection and it persisted for more than 60 days. Histological analysis of postmortem neck tissue revealed no persistent inflammatory response or muscle pathology in the area of acid injection. Control rats that underwent identical injections with physiologically neutral saline had no changes in nociceptive responding. These preliminary findings suggest that trauma to the neck can lead to chronic and diffuse changes in nociceptive processing, even after the acute injury has healed, as has been noted in conditions such as fibromyalgia.
S Datta, K Chattejee, R Kline, R Wiley; Tennessee Valley Healthcare System, Nashville, TN Society for Neuroscience abstract
(113) Pregabalin attenuates mechanical and cold allodynia in Zucker diabetic fatty rats
(115) Involvement of sex hormones in a mice model of neuropathic pain
S Dima, M Urban, E Crown; Merck, West Point, PA Painful diabetic neuropathy is the most common known cause of neuropathy worldwide. Its prevalence is increasing rapidly as the rate of obesity rises in industrialized countries. This study used the Zucker diabetic fatty (ZDF) rat, a commonly used rat model of Type 2 diabetes, to evaluate the development of thermal and mechanical hypersensitivity and the effect of pregabalin on established painful neuropathy. Beginning at 9-weeks of age ZDF rats developed significant hyperglycemia compared to Zucker lean (ZL) controls (ZDF 369.5 ⫹/- 10.8 mg/dl, ZL 95.2 ⫹/- 1.3 mg/dl). Weekly behavioral testing showed no difference between groups for mechanical hyperalgesia (paw pinch test ZDF 200.8 ⫹/11.7 g, ZL 166.0 ⫹/- 4.5 g, 12 weeks of age) but ZDF rats had significantly lower withdrawal thresholds when measured for mechanical allodynia (von Frey test ZDF 5.8 ⫹/- 1.3 g, ZL 13.8 ⫹/- 0.8 g, 12 weeks of age p⬍0.001). Response latencies in ZDF rats were shorter compared to ZL rats for both hot (50¢aC hot plate ZDF 23.6 ⫹/- 2.6 s, ZL 40.2 ⫹/- 1.7 s at 11 weeks, p⬍0.05) and cold (5¢aC cold plate ZDF 25.1 ⫹/- 1.9 s, ZL 49.0 ⫹/4.7 s at 11 weeks, p⬍0.05) stimuli. Pregabalin (20 mg/kg PO) partially reversed the hypersensitivity to both mechanical and cold allodynia in ZDF rats (von Frey ZDF 4.4 ⫹/- 1.8 g pre-dose to 10.3 ⫹/- 0.8 g post-dose, p⬍0.05 and cold plate ZDF 28.9 ⫹/- 4.5 s pre-dose to 42.6 ⫹/- 4.3 s post-dose, p⬍0.05, 16 weeks of age) with no changes observed after pregabalin administration in ZL rats. These results demonstrate that ZDF rats develop symptoms of mechanical and cold allodynia that are attenuated by pregabalin administration.
P Robichaud, M Spooner, J Carrier, S Marchand; Universite´ de Sherbrooke, Sherbrooke, QC Differences between males and females in different types of pain are well-established. In a previous study, we demonstrated that sex hormones are responsible for excitatory and inhibitory mechanisms during the formalin test.1 However, the role of sex hormones in neuropathic pain remains elusive. In the present study, a peripheral nerve injury model (chronic constriction injury; CCI) was use to investigate gender differences in neuropathic pain using intact and gonadectomized mice of both sexes. Mice have been tested for mechanical allodynia (von Frey test) and thermal hyperalgesia (Hargreaves test) for up to 30 days (including 28 days post-CCI). Since we previously demonstrated that endogenous pain inhibitory mechanisms differ between sexes, a stress induced analgesia test (swim test) was also performed on our groups. Since glial cells are known to be involved in the development of neuropathic pain, a spinal marker of glial cells (GFAP) was studied to complement behavioural results. Animals with CCI presented more pain and a higher density of glial cells than controls. In accordance with our previous results with the formalin test, females have a lower pain threshold than males in both allodynia and hyperalgesia. Furthermore, castrated males have more pain and for a longer period of time than intact males, suggesting that testosterone plays a protective role in pain. Finally, pain inhibitory mechanisms seem to be recruited more efficiently in intact animals than in gonadectomized animals. These results show that sex hormones play an important role in the gender difference observed in neuropathic pain. (1. Gaumond, Brain Res, 2005.)