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631)
S8
Abstracts
(330/631) Sustained morphine exposure enhances both bone cancer-induced pain and bone loss
Paper Session 336: Physiological Influences
A Vardanyan, T King, O Melemedjian, L Majuta, J Lai, F Porreca; University of Arizona, Tucson, AZ Metastatic bone cancer causes severe pain in patients and is primarily treated with strong analgesics such as opiates. A potential concern with this approach is that sustained opiate exposure has been shown to induce paradoxical pain states. We examined the effects of sustained morphine administration on pain and bone loss using a mouse model of bone cancer. Murine osteolytic sarcoma cells were injected directly into the femur and sealed in with dental amalgam. Starting 7 days after femoral injection, mice received sustained morphine or saline administration through subcutaneous osmotic mini-pumps. Rather than eliciting antinociception over this time-course, morphine enhanced both sarcoma-induced spontaneous and evoked pain behaviors with a corresponding increase in the expression of pronociceptive neurotransmitters such as SP and CGRP in the DRG. Morphine increased sarcomainduced expression of ATF-3, a marker for damaged cells. Surprisingly, sustained morphine accelerated sarcoma-induced bone destruction and increased the rate of spontaneous fracture. Morphine did not alter tumor growth in vitro or tumor burden in vivo, suggesting the possibility of enhanced osteoclast activity. Consistent with this possibility, sarcomainduced osteoclast activity was upregulated after sustained morphine. Additionally, IL-1 (a proinflammatory cytokine that plays an important role in osteoclastogenesis and peripheral nociceptor sensitization) protein levels were also increased within exudate from the intramedullary space of the bone of sarcoma treated animals 5 days into morphine infusion. These data indicate that sustained exposure to morphine enhances bone cancer-induced pain and increases bone loss, raising questions regarding the appropriate treatment for bone cancer pain. This work is supported by Arizona Disease Research Commission 9007 and DA16431.
B07 - Endogenous Pain Modulation (336/644) Does in-vivo catastrophizing engage descending modulation of spinal nociception? L Maynard, J Russell, K McCabe, A Williams, J Rhudy; The University of Tulsa, Tulsa, OK Catastrophizing has been found to correlate with pain report, but not nociceptive flexion reflex (NFR) threshold suggesting catastrophizing does not engage descending modulation of spinal nociception (France et al., 2002, Pain). However, recent evidence suggests that in-vivo assessment of catastrophizing (assessed during or just following rather than before the noxious event) is a better predictor of pain outcomes (Edwards et al., 2005, J Pain). Given that France et al. assessed catastrophizing prior to the noxious event, it is unclear whether in-vivo catastrophizing is associated with spinal nociception. To examine this issue, we combined data from two recent NFR studies conducted by our laboratory. Every participant (N⫽78) filled out questionnaires assessing depression, self-efficacy for pain, and current mood before noxious stimulation. Then, NFR threshold and pain ratings were assessed by noxious electric stimulation to the sural nerve. NFR threshold was defined as the stimulus intensity that elicited a withdrawal response in the ipsilateral biceps femoris muscle. Pain ratings of threshold-level stimuli were assessed using a numerical rating scale (NRS). Catastrophizing was assessed following the NFR assessment using the Coping Strategies Questionnaire (CSQ). NFR threshold and pain ratings were predicted from catastrophizing scores using hierarchical regression analyses that controlled for gender, self-efficacy, depression, and current mood. Results are consistent with the findings of France et al. suggesting that catastrophizing predicts pain ratings (R square change⫽.07, p⫽.02; Beta⫽.290), but not NFR threshold (R square change⫽.003, p⫽.62, Beta⫽.063). No other predictors were significant in either model (ps⬎.25). Therefore, in-vivo catastrophizing does not appear to engage descending modulation of spinal nociception.
(330/632) Acute adjuvant induced arthritis pain measured in the mouse TMJ
C. Disease Entities (Human)
B Hutchins, R Hinkle, P Kramer, L Bellinger; Baylor College of Dentistry, Texas A&M University System HSC, Dallas, TX Previous studies indicated that local injections of complete Freund’s adjuvant (CFA) into the temporomandibular joint (TMJ) increased the time it takes for a rat to eat a meal. When CFA was injected into the knee joint the meal duration remained constant but meal number decreased. These results suggested that measurements of meal duration are specific for TMJ joint pain (Kerins et al., Int J Oral Maxillofac Surg., 2005). We report here similar experiments in an arthritically sensitive mouse model DBA/1J. In these experiments we bilaterally injected the TMJ of 8 anesthetized mice with 25 micrograms/5 l CFA. Computerized measurements of meal patterns and body weight were analyzed before and after injection. Controls received no injection. Results show a decrease in 24h food intake after TMJ injection and food intake remained significantly lower for two days in the CFA injected animals when compared to controls (Day 1: 2.1⫾0.4g vs 4.4⫾0.3g; Day 2: 3⫾0.2g vs 4.1⫾0.3g, Pⱕ0.05). This initial decrease in food intake was due solely to a decrease in meal number (Day 1: 11.3⫾2.4 vs 22.3⫾2; Day 2: 14.6⫾0.1.2 vs 19.6⫾1.4, Pⱕ0.05). Interestingly, six and seven days after CFA injection meal duration significantly increased (Day 6:12.2⫾2min vs 7⫾0.9min; Day 7: 12.6⫾2.5 min vs 6⫾0.4min, Pⱕ0.05). We conclude that the dose of CFA utilized initially induced a systemic effect causing illness in the whole animal lowering meal number. After 5 days, the animals appeared to return to normal as their meal number and food intake were no different when compared to controls. However, following 6/7 days, the adjuvant-induced TMJ pain and inflammation resulted in longer meal duration consistent with our previously published results in rats. Supported by the NIH/NIDCR DE07188, DE016059, DE015372, Baylor College of Dentistry Intramural Grant Program, and the Baylor Oral Health Foundation.
C07 - Myofascial Pain & Fibromyalgia (336/695) Psychiatric comorbidities in a community sample of women with fibromyalgia K Raphael, M Janal, S Nayak, J Schwartz, R Gallagher; UMDNJ-New Jersey Medical School, Newark, NJ Prior studies often conclude that the risk of major depressive disorder (MDD) and other psychiatric disorders is elevated in fibromyalgia (FM), but these studies have been conducted among care-seeking patients in whom the risk of psychiatric disorder may be over-represented. The current investigation utilizes state-of-the-art diagnostic procedures for both FM and psychiatric disorders to estimate prevalence rates of FM in a diverse community sample of women, and to estimate the community comorbidity of FM and specific psychiatric disorders. Participants were screened by telephone for FM and MDD, by selecting telephone numbers at random from a list of households with women in the NY/NJ metropolitan area. Eligible women were invited to complete physical examinations for FM and clinician-administered psychiatric interviews. Data were weighted to adjust for sampling procedures and population demographics in the recruitment areas. The estimated overall prevalence of FM among women in the NY/NJ metropolitan area was 3.7% (95% CI ⫽ 3.2, 4.4), with elevated rates detected among racial minorities. Although the risk of current MDD was nearly three times higher in women with versus without FM, the risk of lifetime MDD was similar in these two groups of community women. Interestingly, the risk of lifetime anxiety disorders, particularly obsessive compulsive disorder and post traumatic stress disorder, was approximately five-fold higher in community women with FM. Overall, this study found a prevalence for FM among women that is consistent with prior North American community studies, and revealed that FM is even more prevalent among minority women in the community. These community-based data also indicated that the relationship between MDD and FM may be even more complicated than previously thought, and call for an increased focus on anxiety disorders in FM.
Abstracts
(330/631) Sustained morphine exposure enhances both bone cancer-induced pain and bone loss
Paper Session 336: Physiological Influences
A Vardanyan, T King, O Melemedjian, L Majuta, J Lai, F Porreca; University of Arizona, Tucson, AZ Metastatic bone cancer causes severe pain in patients and is primarily treated with strong analgesics such as opiates. A potential concern with this approach is that sustained opiate exposure has been shown to induce paradoxical pain states. We examined the effects of sustained morphine administration on pain and bone loss using a mouse model of bone cancer. Murine osteolytic sarcoma cells were injected directly into the femur and sealed in with dental amalgam. Starting 7 days after femoral injection, mice received sustained morphine or saline administration through subcutaneous osmotic mini-pumps. Rather than eliciting antinociception over this time-course, morphine enhanced both sarcoma-induced spontaneous and evoked pain behaviors with a corresponding increase in the expression of pronociceptive neurotransmitters such as SP and CGRP in the DRG. Morphine increased sarcomainduced expression of ATF-3, a marker for damaged cells. Surprisingly, sustained morphine accelerated sarcoma-induced bone destruction and increased the rate of spontaneous fracture. Morphine did not alter tumor growth in vitro or tumor burden in vivo, suggesting the possibility of enhanced osteoclast activity. Consistent with this possibility, sarcomainduced osteoclast activity was upregulated after sustained morphine. Additionally, IL-1 (a proinflammatory cytokine that plays an important role in osteoclastogenesis and peripheral nociceptor sensitization) protein levels were also increased within exudate from the intramedullary space of the bone of sarcoma treated animals 5 days into morphine infusion. These data indicate that sustained exposure to morphine enhances bone cancer-induced pain and increases bone loss, raising questions regarding the appropriate treatment for bone cancer pain. This work is supported by Arizona Disease Research Commission 9007 and DA16431.
B07 - Endogenous Pain Modulation (336/644) Does in-vivo catastrophizing engage descending modulation of spinal nociception? L Maynard, J Russell, K McCabe, A Williams, J Rhudy; The University of Tulsa, Tulsa, OK Catastrophizing has been found to correlate with pain report, but not nociceptive flexion reflex (NFR) threshold suggesting catastrophizing does not engage descending modulation of spinal nociception (France et al., 2002, Pain). However, recent evidence suggests that in-vivo assessment of catastrophizing (assessed during or just following rather than before the noxious event) is a better predictor of pain outcomes (Edwards et al., 2005, J Pain). Given that France et al. assessed catastrophizing prior to the noxious event, it is unclear whether in-vivo catastrophizing is associated with spinal nociception. To examine this issue, we combined data from two recent NFR studies conducted by our laboratory. Every participant (N⫽78) filled out questionnaires assessing depression, self-efficacy for pain, and current mood before noxious stimulation. Then, NFR threshold and pain ratings were assessed by noxious electric stimulation to the sural nerve. NFR threshold was defined as the stimulus intensity that elicited a withdrawal response in the ipsilateral biceps femoris muscle. Pain ratings of threshold-level stimuli were assessed using a numerical rating scale (NRS). Catastrophizing was assessed following the NFR assessment using the Coping Strategies Questionnaire (CSQ). NFR threshold and pain ratings were predicted from catastrophizing scores using hierarchical regression analyses that controlled for gender, self-efficacy, depression, and current mood. Results are consistent with the findings of France et al. suggesting that catastrophizing predicts pain ratings (R square change⫽.07, p⫽.02; Beta⫽.290), but not NFR threshold (R square change⫽.003, p⫽.62, Beta⫽.063). No other predictors were significant in either model (ps⬎.25). Therefore, in-vivo catastrophizing does not appear to engage descending modulation of spinal nociception.
(330/632) Acute adjuvant induced arthritis pain measured in the mouse TMJ
C. Disease Entities (Human)
B Hutchins, R Hinkle, P Kramer, L Bellinger; Baylor College of Dentistry, Texas A&M University System HSC, Dallas, TX Previous studies indicated that local injections of complete Freund’s adjuvant (CFA) into the temporomandibular joint (TMJ) increased the time it takes for a rat to eat a meal. When CFA was injected into the knee joint the meal duration remained constant but meal number decreased. These results suggested that measurements of meal duration are specific for TMJ joint pain (Kerins et al., Int J Oral Maxillofac Surg., 2005). We report here similar experiments in an arthritically sensitive mouse model DBA/1J. In these experiments we bilaterally injected the TMJ of 8 anesthetized mice with 25 micrograms/5 l CFA. Computerized measurements of meal patterns and body weight were analyzed before and after injection. Controls received no injection. Results show a decrease in 24h food intake after TMJ injection and food intake remained significantly lower for two days in the CFA injected animals when compared to controls (Day 1: 2.1⫾0.4g vs 4.4⫾0.3g; Day 2: 3⫾0.2g vs 4.1⫾0.3g, Pⱕ0.05). This initial decrease in food intake was due solely to a decrease in meal number (Day 1: 11.3⫾2.4 vs 22.3⫾2; Day 2: 14.6⫾0.1.2 vs 19.6⫾1.4, Pⱕ0.05). Interestingly, six and seven days after CFA injection meal duration significantly increased (Day 6:12.2⫾2min vs 7⫾0.9min; Day 7: 12.6⫾2.5 min vs 6⫾0.4min, Pⱕ0.05). We conclude that the dose of CFA utilized initially induced a systemic effect causing illness in the whole animal lowering meal number. After 5 days, the animals appeared to return to normal as their meal number and food intake were no different when compared to controls. However, following 6/7 days, the adjuvant-induced TMJ pain and inflammation resulted in longer meal duration consistent with our previously published results in rats. Supported by the NIH/NIDCR DE07188, DE016059, DE015372, Baylor College of Dentistry Intramural Grant Program, and the Baylor Oral Health Foundation.
C07 - Myofascial Pain & Fibromyalgia (336/695) Psychiatric comorbidities in a community sample of women with fibromyalgia K Raphael, M Janal, S Nayak, J Schwartz, R Gallagher; UMDNJ-New Jersey Medical School, Newark, NJ Prior studies often conclude that the risk of major depressive disorder (MDD) and other psychiatric disorders is elevated in fibromyalgia (FM), but these studies have been conducted among care-seeking patients in whom the risk of psychiatric disorder may be over-represented. The current investigation utilizes state-of-the-art diagnostic procedures for both FM and psychiatric disorders to estimate prevalence rates of FM in a diverse community sample of women, and to estimate the community comorbidity of FM and specific psychiatric disorders. Participants were screened by telephone for FM and MDD, by selecting telephone numbers at random from a list of households with women in the NY/NJ metropolitan area. Eligible women were invited to complete physical examinations for FM and clinician-administered psychiatric interviews. Data were weighted to adjust for sampling procedures and population demographics in the recruitment areas. The estimated overall prevalence of FM among women in the NY/NJ metropolitan area was 3.7% (95% CI ⫽ 3.2, 4.4), with elevated rates detected among racial minorities. Although the risk of current MDD was nearly three times higher in women with versus without FM, the risk of lifetime MDD was similar in these two groups of community women. Interestingly, the risk of lifetime anxiety disorders, particularly obsessive compulsive disorder and post traumatic stress disorder, was approximately five-fold higher in community women with FM. Overall, this study found a prevalence for FM among women that is consistent with prior North American community studies, and revealed that FM is even more prevalent among minority women in the community. These community-based data also indicated that the relationship between MDD and FM may be even more complicated than previously thought, and call for an increased focus on anxiety disorders in FM.