Adenylate cyclase inhibition attenuates neuropathic pain but lacks pre-emptive effects in rats.

PURPOSE: There is evidence that cyclic adenosine monophosphate (cAMP) transduction is involved in nociceptive processing. We previously showed that intrathecal injection of an adenylate cyclase inhibitor attenuated tactile allodynia caused by partial sciatic nerve ligation (PSNL) in rats. The present study investigates the pre-emptive effects of spinal cAMP transduction on nociceptive processing in a chronic neuropathic pain model. METHODS: Intrathecal catheterization and PSNL were performed in male Sprague-Dawley rats. Nociceptive responses to mechanical and thermal stimuli were evaluated at the hindpaw at 2 hr and at 3, 7, and 14 days after PSNL. The pre-emptive effects of the intrathecal adenylate cyclase inhibitor, SQ22536 (0.7 mumol x L(-1), 30 min before or after nerve ligation) were assessed. Also, the spatial and temporal expression profiles and immunoreactivity in the spinal cord of the cAMP response element binding protein (CREB) and its phosphorylated proteins (CREB-IR and p-CREB-IR) were analyzed. RESULTS: Compared with the rats treated with the vehicle, allodynia and hyperalgesia were significantly attenuated at 1-3 days by the intrathecal injection of SQ22536 performed either before or after ligation. The expression of CREB was significantly higher after ligation (P < 0.05), but differences were not observed between groups. Intrathecal injection of SQ22536, either before or after ligation, partially reduced p-CREB-IR protein expression in comparison with the vehicle control, especially after the first 3 days (P < 0.05). CONCLUSION: Our results show a possible association between the increase in p-CREB and PSNL-induced neuropathic pain. However, a pre-emptive effect of adenylate cyclase inhibitor administered before surgery was not observed.

Inhibition of the cyclic adenosine monophosphate pathway attenuates neuropathic pain and reduces phosphorylation of cyclic adenosine monophosphate response element-binding in the spinal cord after partial sciatic nerve ligation in rats.

BACKGROUND: Recent reports have identified a role for cyclic adenosine monophosphate (cAMP) transduction in nociceptive processing. Spinal activation of the cAMP induced gene transcription through the activation of protein kinase A and cAMP response element-binding protein (CREB). Intrathecal injection of protein kinase A inhibitor reversed the mechanical hyperalgesia, whereas injection of CREB antisense attenuated tactile allodynia caused by partial sciatic nerve ligation (PSNL) in rats. In the present study, we aimed to assess the effects of spinal cAMP transduction on the nociceptive processing in a chronic neuropathic pain model. METHODS: PSNL was performed in male Sprague-Dawley rats 1 wk after intrathecal catheterization. Nociception to mechanical and thermal stimuli was assessed at the hindpaw 2 h, 3, 7, and 14 days after PSNL. The effects of adenylate cyclase inhibitor, SQ22536 (0.7 mumol, intrathecal) on these nociceptions were evaluated. Changes in the expression and immunoreactivity of CREB and its phosphorylated proteins (CREB-IR and pCREB-IR) in the dorsal horn of the spinal cord were also measured. RESULTS: The expression of CREB-IR and pCREB-IR proteins was shown to increase for 2 wk after PSNL. The increase in pCREB was partially reversed by the blockade of the cAMP pathway in the early 3 days, with a parallel increase in mechanical and thermal withdrawal thresholds. CONCLUSION: These results revealed the possible contribution of an increase in pCREB to the PSNL-induced tactile allodynia and thermal hyperalgesia. Modulation of the cAMP pathway may be clinically relevant if early intervention can be achieved in patients with chronic neuropathic pain.

Broken needle in the cervical spine: a previously unreported complication of Xiaozendao acupuncture therapy.

Xiaozendao (meaning "small-needle-knife," in Chinese) is a form of alternative medical instrument shaped like an acupuncture needle with a flat edge on the needle tip. It is widely used for the treatment of many different disorders in Asian countries, especially in the People's Republic of China. Its use has gained increasing popularity. To our knowledge, there are no reports of practitioners' experiences or adverse events related to "small-needle-knifed" therapy until now. We reported the first case of spinal-cord injury with delayed onset of neurologic symptoms from a broken small-needle-knife insertion into the spinal cord.

Successful use of iv diltiazem to control perioperative refractory complex atrial tachyarrhythmias in a patient with pneumoconiosis.

PURPOSE: To present a patient with pneumoconiosis who developed a complex, life-threatening atrial tachyarrhythmia during anesthesia. Intravenous diltiazem was effective in controlling the ventricular rate and hemodynamics after failure of other antiarrhythmic drugs and direct current cardioversion. CLINICAL FEATURES: A 79-yr-old man with pneumoconiosis complicated by cor pulmonale suffered from gout-related cellulitis of the left lower limb. Debridement of the left gangrenous big toe was carried out under general anesthesia. During anesthesia, a wide-QRS tachycardia occurred suddenly and a complex atrial tachyarrhythmia was later diagnosed. Hemodynamics deteriorated despite aggressive treatment with lidocaine, verapamil, direct current cardioversion, magnesium, digoxin and amiodarone. Correction of the underlying respiratory acidosis was not sufficient to control the rapid ventricular response. Eventually, iv diltiazem adequately controlled the rapid ventricular rate and quickly improved the deteriorating hemodynamics. CONCLUSION: Life-threatening complex atrial tachyarrhythmias may occur in patients with chronic lung diseases perioperatively. Intravenous diltiazem was effective in the management of complex atrial tachyarrhythmia in a patient with underlying cor pulmonale.