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complex regional pain syndrome ( crps ) type ii , known as causalgia , develops after a nerve injury , and tends to show the more painful and more severe symptoms of crps .
the ordinary strategy in crps treatment is often multi - disciplinary , with the use of various kinds of medications and physical therapies combined with sympathetic nerve block .
even with several treatments , it is very difficult to manage the acute stage of crps type ii . and
neurostimulation ( spinal cord stimulator ) could be surgically implanted to control the pain by directly stimulating the spinal cord for the treatment of intractable crps .
a systematic review concluded that spinal cord stimulation appears to be an effective therapy in the management of patients with crps type i ( level a evidence ) than type ii ( level d evidence)14 ) .
moreover , there is evidence to reveal that scs is a cost - effective treatment for crps type i. we report a case of acute stage crps type ii treated with new anti - inflammatory agent [ polydeoxyribonucleotide ( pdrn ) solution ] .
as far as we know , this is 1st case report showing effectiveness of pdrn for the treatment of crps type ii .
a 32-year - old female patient came to the hospital complaining of left leg numbness .
she had experienced a traumatic event , a fall into a waterway , one month ago .
after which , she had severe low back pain and was evacuated to the nearby general hospital . computed tomography ( ct ) showed an l5 left transverse process fracture and an s2 body fracture , and absolute bed rest ( abr ) for one month was recommended ( fig .
her left leg numbness was progressively aggravated . to evaluate whether symptom aggravation during the abr period was related to the patient 's history of a left - side l5s1 discectomy 2 years previously
the mri did not show recurrent disc material , but it did show an annular tear at l45 and postoperative scar tissue at l5s1 , and the previous doctor recommended continued conservative management . after the period of abr was complete , the patient began ambulation and was transferred to our hospital in her hometown .
she complained of left leg numbness initially upon arrival , and the more she walked , the more the pain was aggravated , showing hyperalgesia and allodynia .
even as the symptoms seemed to subside somewhat , skin flushing still appeared on the left lower leg when the patient was in a standing position ( fig .
2 ) . the persistent skin discoloration seemed to worsen as time went on , despite frequent sympathetic nerve blocks using steroid .
to rule out the possibility of arterial injury , we performed lower extremity ct angiography , and there was no sign of arterial injury around the fracture site .
we concluded that her symptoms resulted from lumbosacral plexus injury due to the transverse process fracture . at that time
, it was 2 months after the initial trauma . because this was the acute phase , we wanted to prevent the disease from progressing to the chronic phase .
our clinics have been performing prolotherapy using pdrn solution , and we are familiar with the effects of pdrn .
we injected pdrn solution at the ventral surface of the left l5 transverse process , superior and inferior , one ampoule ( 3 cc ) each by using needles used for medial branch block ( fig .
allodynia and hyperalgesia were improved one day after the procedure and the skin flushing was diminished ( fig .
the patient was discharged 3 days after the pdrn injection and at the 1-month follow - up , her symptoms were very much improved .
autonomic disturbance can lead to significant pain in patients with peripheral nerve injuries and is characteristic of crps .
severe burning pain , allodynia , hyperalgesia , careful attempts to protect the involved extremity from movement or contact , and evidence of autonomic hyper- or hypoactivity are features of crps .
vascular changes such as skin flushing and discoloration and temperature fluctuations are hallmarks of this deranged autonomic activity .
crps type i usually occurs after a minor injury to the extremity ( e.g. , ankle sprain ) , whereas crps type ii occurs after significant injury to a major mixed nerve ( e.g. , brachial plexus injury ) , such as in our case .
crps may change within a patient over time , particularly in the transition from " warm crps " ( acute ) to " cold crps " ( chronic)5 ) .
several pathophysiological concepts have been proposed to explain the complex symptoms of crps : 1 ) facilitated neurogenic inflammation ; 2 ) pathological sympatho - afferent coupling ; and 3 ) neuroplastic changes within the cns11 ) .
management of crps remains challenging , with many patients having only partial or minimal relief with treatment .
pharmacotherapy is based on individual symptoms and includes steroids , free radical scavengers , antineuralgic agents , and finally agents interfering with bone metabolism ( calcitonin , bisphosphonates ) .
nonsteroidal anti - inflammatory drugs ( nsaids ) , corticosteroids , cyclooxygenase ( cox)-2 inhibitors , and free radical scavengers are used in crps with intent to treat for pain as well as for inflammation .
however , crps - related inflammation may be largely neurogenic , initiated by inflammatory mediators from the terminals of afferent nociceptors , and no drugs have been studied for this type of inflammation8 ) .
sympathetic nerve block is traditionally recognized as an important procedure , both in the diagnosis and treatment of crps .
the pain relief following sympathetic nerve block generally outlasts the effect of the local anesthetic13 ) .
if after numerous therapies , a patient 's pain is intractable , sympathectomy or spinal cord stimulation ( scs ) may be recommended as surgical treatment alternatives .
recently , scs seems to be the general trend , and it is reported that scs is effective in reducing the chronic neuropathic pain of crps type i914 ) .
specific treatment of crps type ii at the chronic stage is also reported , but to our knowledge , no specific interventional or invasive treatment for control of acute stage crps type ii has been reported6 ) .
pdrn ( placentex ) is a low molecular weight dna complex extracted from trout sperm .
the adenosine a2a receptor alters the cytokine system by decreasing secretion of inflammatory cytokines such as tumor necrosis factor- , macrophage inflammatory protein 1 , and interleukin ( il)-6 .
the adenosine a2a receptor is also associated with increased circulation of il-10 , anti - inflammatory cytokine4 ) .
therefore , pdrn has an anti - inflammatory effect and could be a potential pharmacological treatment for inflammatory diseases such as rheumatoid arthritis315 ) .
this also explains how pdrn can help to control the acute phase of crps , such as in our case .
however , this does n't seem to be enough to explain the dramatic result of our case .
the adenosine a2a receptor also has a tissue regeneration effect , as indicated by its stimulation of endothelial cell migration and proliferation .
activation of this receptor is also associated with increased levels of vascular endothelial growth factor , which enhances tissue function712 ) . promoting cell proliferation by acting as a mitogen for fibroblasts and
, endothelial cells could result in extracellular matrix production and remodeling , and can be useful for burn treatment and prolotherapy210 ) .
we suppose that this regeneration mechanism has an additional effect on our case . because we have been performing prolotherapy in our clinics , we have observed these mechanisms of pdrn , not only the regeneration effect , but also the anti - inflammatory effect .
pdrn has been found to be a safe modality , and no harmful effect has been reported1 ) .
patients with acute stage crps type ii need appropriate treatment to prevent progression to the chronic phase .
treatment is based on a multidisciplinary approach , and pdrn could be an option for the treatment of the acute inflammatory phase of crps type ii .
complex regional pain syndrome ( crps ) type ii is a syndrome that develops after nerve injury . 
 symptoms may be severe , and vary depending on the degree of sympathetic nerve involvement . as 
 yet , there is no satisfactory treatment . 
 we report the case of a female patient who had an l5 left transverse process fracture and an s2 body fracture , who developed symptoms of crps type ii in her left lower leg that were aggravated during ambulation in spite of absolute bed rest for one month after the trauma . 
 several treatments , including bed rest , medication , and numerous nerve blocks were attempted , but the pain persisted . 
 we finally tried injection of polydeoxyribonucleotide ( pdrn ) solution at the left l5 transverse process fracture site because we knew of the anti - inflammatory effect of pdrn . 
 one day after this treatment , her symptoms had almost disappeared and three days later , she was discharged . 
 we will also further discuss the possibility of using pdrn solution for the treatment of crps .