Feasibility Study of New Method of Diagnostic and Prediction of Painful CIPN
Phase: NA
Conditions: Burning Pain, Impaired Balance, Malignant Ovarian Neoplasm, Numbness, Peripheral Neuropathy, Pain, Acute, Tingling
Sponsor: Stanford University

7,7/(Feasibility Study of New Method of Diagnostic and Prediction of Painful CIPN
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Yevgenie (Gene) Kazinetz, PhD 
 
Sponsor 
NIH/NCI SBIR  
 
Small Business Collaborator 
LasMed, LLC 
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Painful peripheral neuropathy (PPN) is a common sequela of chemotherapy that severely impacts 
the quality of life in cancer patients (1). There is no biomarker, tool, or method to predict the 
development or progression of painful chemotherapy-induced peripheral neuropathy (CIPN). 
The pathophysiology of CIPN remains insufficiently understood; current treatment and 
prevention strategies provide only modest benefit to patients (2).  In this study, we will test the 
utility of the Diode Laser fiber type Selective Stimulator (DLss) (3) in identifying patients at risk 
of developing PPN. 
 
Small-diameter lightly myelinated Aδ and unmyelinated C cutaneous nociceptive fibers transmit 
pain from the peripheral to central nerve system. Aδ and C fibers are divided by sensitivity: heat, 
mechanical (tactile), and chemical stimulation, and epidermal versus dermal location. In animals 
and humans, dying back intra-epidermal fibers lead to reduced pain sensitivity, rather than pain, 
which suggests fiber loss alone is not sufficient to explain the development of neuropathic pain 
(4-9). In contrast, abnormally high spontaneous activity of nociceptive fibers, specifically dermal 
C mechano-insensitive (CMi) fibers, is associated with peripheral ongoing neuropathic pain (10-
12)((13-15). Therefore, a tool that can measure, track, and predict the development of abnormal 
function of Aδ and C fibers is a critical unmet medical need. 
 
Most diagnostic tests to study nociceptive fibers are able to measure the loss of pain sensitivity in 
epidermal fibers (4-9). However, these tests are not fiber-type selective (11). Only 
microneurographic recording is able to separate fiber type and to access single fibers (16). 
Though due to complexity, microneurography is unpractical in the clinic. In contrast, we 
developed and patented DLss, which can be used at the bedside to safely and selectively 
stimulate Aδ and C fibers in superficial and deep skin(14-23). Our preliminary DLss data 
demonstrates that patients with painful CIPN, who have decreased epidermal Aδ and C-fiber 
densities, have increased Aδ pain thresholds, while C-fiber thresholds are intact (20). The Aδ:C 
pain threshold ratio was consistently higher in CIPN than healthy volunteers.  
 
Based on these preliminary data, we propose that the Aδ:C pain threshold ratio, as measured by 
the DLss during chemotherapy, will identify those patients at risk of developing pain during 
their treatment. Ultimately, this will help us identify patients who 1) may benefit from a change 
in their treatment to prevent CIPN and 2) patients who would be the best candidates for 
interventional trials testing new drugs for the prevention of PPN. 
 
Aim 1: Demonstrate that the Aδ:C pain threshold ratio is significantly higher in patients 
with painful CIPN than in patients with painless CIPN. 
Ovarian cancer annually affects about 20,000 women in the US and causes 14,000 deaths (1999–
2012 Cancer Incidence and Mortality Data, http://www.cdc.gov/cancer/ovarian/statistics/) (24) 
Ovarian cancer patients’ first line chemotherapy regimen is typically a taxane combined with 
platinum. These drugs are known to cause CIPN neuropathic symptoms in up to 70% of patients; 
a large portion of those patients develop painful CIPN (25, 26). The combination of taxane with 
platinum may increase development of CIPN in 1.5 times compared to just taxane 
application(25). As a result, ovarian cancer patients have a high overall burden of painful CIPN. 
Though the exact mechanism of nerve damage may differ between taxanes and platinum drugs, 
they both result in painful CIPN. Here we will examine the underlying shared pathophysiology 

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of neuropathic pain. We will evaluate the DLss in [64] ovarian cancer patients with painful and 
painless neuropathy during initial taxane combined with platinum treatment, to determine their 
Aδ:C pain threshold ratios. Presence or absence of pain will be determined via pain questionnaire 
and numeric pain scale (27). Enrolling 25 patients with painful CIPN and 25 patients with 
painless CIPN, we will have 80% power to detect a 1.31 fold Aδ:C pain threshold ratio. 
 
Aim 2: Determine the Aδ:C ratio over time in patients with CIPN. 
Our early data suggests a relationship between pain and the Aδ:C ratio in patients where pain is a 
well-established problem. However, the time course for development and sustainment of CIPN 
(painful and painless) is not well described. Early changes in the Aδ:C ratio may predict 
progression of CIPN during the course of the treatment  and which patients will develop long-
term neuropathy; or alternatively, the Aδ:C ratio may not change until weeks to months after 
symptoms have developed, analogous to the delay seen in EMG in mild–moderate nerve damage 
(28). Following patients longitudinally will also allow us to correlate Aδ:C ratio changes with the 
initial ratio, the patient’s perception of pain over time, total dose of taxane and platinum, and 
possibly, treatments for neuropathic pain. Patients will be offered retesting approximately two 
weeks after the completion of sixth cycle.  Aδ:C ratio changes will be correlated with 
progression of CIPN based on the presence or absence of pain and dose of agents to determine if 
the Aδ:C ratio evolves with symptoms and if a change in ratio predicts the progression to chronic 
painful neuropathy, chronic painless neuropathy, or resolution of symptoms. 
 
The proposed work will provide valuable information about the development of pain in CIPN 
caused by common chemotherapies use to treat ovarian, colon, and other cancers. It will provide 
the basis for a larger study to validate the utility of DLss as a noninvasive bedside test for small-
fiber neuropathies and provide a tool for investigators and clinicians to track and predict the 
development of pain in CIPN.  
 
2.0  
BACKGROUND AND RATIONALE  
Peripheral neuropathy is a common side effect of chemotherapy, occurring in more than 60% of 
patients at some point during the course of cancer treatment (1). The resulting pain, numbness, 
and weakness can severely diminish quality of life. For many patients, the development of 
neuropathy leads to dose reduction or/and treatment delay, which may ultimately impact 
survival. The mechanisms by which chemotherapy-induced nerve damage ultimately leads to 
pain are poorly understood. As a result, there is no reliable way to predict which patients will 
develop irreversible painful chemotherapy-induced peripheral neuropathy (CIPN)(29-31) and 
consequently, no effective preventative strategy for combating it. The NIH (PA-12-083) has 
recognized this gap. This SBIR-funded project proposes the use of a new, patented, noninvasive 
test to interrogate specific subtypes of small diameter nerve fibers in patients with CIPN, 
addressing the need for an early diagnostic tool and ultimately predicting which patients should 
be offered early intervention to prevent persistent painful CIPN.  
 
Two types of nerve fibers found within the epidermal and dermal skin layers, lightly myelinated 
Aδ and small unmyelinated C fibers, transmit nociceptive (pain) information. In certain types of 
painful neuropathy, such as painful diabetic neuropathy and CIPN, there is a dramatic dying back 
or degradation of these epidermal fibers (6, 32-34). Despite symptoms of pain, these patients 
have significantly increased pain thresholds when tested with currently available methods, which 

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primarily activate epidermal fibers, such as the CO2 laser or contact heat thermodes (6, 7). In 
experimental models, ablation of the nociceptive fibers leads to loss of pain sensitivity, rather 
than pain, suggesting nerve fiber loss alone is not sufficient to explain the development of pain 
(35).  
 
In contrast, spontaneous activity of small fibers is associated with painful peripheral neuropathy 
(PPN) in animals and humans (13-15). Recently, a specific subtype of C fibers, the C mechano-
insensitive (CMi) fibers, was found to be spontaneously active in patients with painful CIPN (14) 
as well as in other types of PPN (16). CMi fibers are located primarily in the dermis, have widely 
branching afferent arbors, are relatively insensitive to mechanical stimuli, but respond to noxious 
heat and chemicals (10). When activated, these fibers release chemokines that can cause 
vasodilation and may, in turn, sensitize surrounding fibers. In a rat model of paclitaxel-induced 
painful neuropathy, intra-epidermal nerve fiber degeneration was prominent, but deeper sub-
epidermal axon bundles, where CMi reside, were spared (36). These characteristics suggest CMi 
fibers play a critical role in generating peripheral pain in CIPN. 
 
There are several practical limitations to studying small nerve fibers, particularly CMi fibers, in 
patients suffering from CIPN. Current diagnostic tests are invasive, extremely time consuming, 
unable to selectively activate small fiber subtypes, or cannot safely stimulate deep fibers.  
Conventional electromyography and nerve conduction studies only provide information about 
large fibers. Microneurography can reliably distinguish small fiber types but it requires hours of 
invasive testing which is impractical for broad 
clinical use. Skin biopsy can be used to 
quantify small fiber density, but does not 
always correlate with CIPN symptomatology 
(33, 37). Noninvasive techniques, such as the 
QST battery (quantitative sensory testing) 
with radiant heat or contact thermodes or with 
the LEP (laser evoked potentials) based on 
CO2 laser do not selectively activate C versus 
Aδ and can only safely be used to interrogate 
superficially located fibers (38-40) (see 
Figure 1A). CMi fibers require current 
densities five times higher than epidermal 
polymodal nociceptors (11). Similarly, the 
amount of radiant (e.g., non-coherent) heat 
required to activate CMi fibers results in surface 
temperatures that are about 7 °C higher than the 
activation threshold of C polymodal nociceptors 
(11, 41) Consequently, both electrical and radiant heat stimuli activate C polymodal nociceptors 
at intensities well below those for activating CMi fibers, rendering them non-selective and of 
limited use in evaluating CMi status in patients. In other words, currently available psychometric 
tests do not allow for the assessment of CMi fiber function.  Therefore, it is not surprising that 
both psychometric QST and LEP tests of small diameter fibers are neither recommended nor 
reimbursed by Medicare and other insurance companies.  
 
In contrast, the Diode Laser fiber type Selective Stimulator (DLss) selectively stimulates Aδ 
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and C fibers at much greater depths than existing techniques, which makes it an ideal 
method to assess small fiber subtypes separately. Thus, this technology opens the possibility 
for bedside clinical testing of a broad array of small fiber neuropathies. 
 
Preliminary Work 
In a series of 16 patients with PPN (painful diabetic neuropathy and painful CIPN), the DLss Aδ 
fiber protocol revealed significantly increased pain thresholds compared to healthy volunteers, 
but C-fiber protocol pain thresholds were similar to those recorded in healthy volunteers (20). 
This is in distinct contrast to radiant or surface 
heating methods, which produce significantly 
higher heat pain thresholds in DPN patients (6, 
42). The difference in threshold measurements 
between the DLss and other heating methods 
cannot be explained by activation of the same 
fiber type. Instead, it is likely that heat pain 
thresholds measured using the DLss are the result 
of deeper CMi fiber activation, whereas radiant or 
surface heating evokes pain via activation of 
epidermal C polymodal nociceptors (see Figure 
1B). The six patients with painful CIPN tested in 
our small pilot had a statistically significant 
difference in the Aδ:C pain threshold ratio when 
compared patients with normal volunteers (see 
Figure 2). The range of pain stimulation was set 
up from pain detection to mild pain and well 
tolerated by both group of patients. No patients 
withdrew from this study due to pain caused by 
the testing. No healthy patients in these studies 
had a ratio >2. This was a small non-uniform sample and was not powered to detect a change in 
ratios a priori. These preliminary data suggest a robust difference between patients with painful 
CIPN and normal patients. Therefore, we hypothesize that there is a significant relationship 
between the Aδ:C ratio and painful 
CIPN.  
 
 
 
 
 
 
 
In this study, we will test the above 
hypothesis in patients with newly-
diagnosed ovarian cancer, who typically 
Figure 2.  Pain threshold ratio of Aδ to C fibers, 
activated by DLss for 3 patient groups: healthy, 
painful diabetic neuropathy, and painful CIPN. 
P<0.05, one-way ANOVA. 
Figure 1B. Chemotherapy results in damage or 
dying back of Aδ and C nociceptive fibers in the 
epidermis, while dermal fibers are relatively 
spared. The DLss can penetrate into the dermis. 
Sparing the CMi in the presence of damage to Aδ 
results in an increased Aδ:C pain threshold ratio. 

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receive a combination of paclitaxel and carboplatin as first-line chemotherapy. Both drugs 
individually, and in combination, are known to cause painful peripheral neuropathy in a 
proportion of patients. Paclitaxel and carboplatin cause peripheral nerve injury by different 
mechanisms, but both ultimately cause neuropathic pain (43). Because the proposed underlying 
pathophysiology of the pain is shared, we feel comfortable grouping these patients. We propose 
that using the DLss in patients with CIPN will allow for the assessment of changes in small-fiber 
pain thresholds and correlation of these changes to painful versus painless states. Additionally, 
we would like to demonstrate that the DLss correlates with persistent painful neuropathy. Our 
ultimate goal is to develop a non-invasive, bedside quantitative test for CIPN. For practiconers 
and patients, this could help avoid the use of more invasive, time-consuming tests, and non-
small-fiber oriented testing, such as electromyography. If successful, this diagnostic test will also 
be relevant to drug testing, to help identify patients who are more likely to benefit from an 
intervention (44). The DLss could also be used to monitor the results of such trials noninvasively 
in a clinical and preclinical setting. While this study focuses on ovarian cancer patients, taxane 
and platinum based regimens are first-line treatment for several cancer types including ovarian, 
breast, lung, and colon cancer; therefore it is expected that the developed clinical test will be 
useful for these patients as well (26).  
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DQG%The Stanford Women’s Cancer Center sees about 150 new cases of ovarian cancer per 
year, therefore we believe will able to complete enrollment in 12 months. Patients will be 
stratified into painful versus painless group based on their first pain assessment inventory. Based 
on the incidence of painful versus painless neuropathy, we anticipate that Group B will complete 
enrollment first. Should enrollment in Group A be very slow, our team will consider advertising 
outside of the Stanford Women’s Cancer Center. An additional approach is to increase 
enrollment in Group B and apply an “unbalanced” design which would increase the number of 
patients in Group B, but still ensure statistical power of 80%.  For example, if only 18 patients 
with pain are identified, enrolling 39 patients without pain will maintain 80% power. If this step 
is needed, we will amend the IRB as well as this application. Additionally, we will apply for a 
no-cost extension to the NIH SBIR that is funding the project. 
 
We understand that patients participating in non-interventional, longitudinal, clinical studies may 
not follow up for a variety of reasons.To address possible drop out, patients will receive higher 
compensation for participation in the second test, 75 dollars for the first, 125 dollars for the 
second. A commonly anticipated drop-out rate is 20% (45), leaving us with approximately 40 
patients who we anticipate will complete both time points within the study timeframe. However, 
it is possible that patients in pain (Group A) may be more likely to follow up with the second 
test, which would help preserve the power of the study. 
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Note that the dose of platinum and/or taxane will be determined by the treating oncologist. No decisions 
about total dose, dose delays, escalations, or reductions will be made based on testing in this protocol. 
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IURP0 to 100, where 0 is no pain and 100 is the worst imaginable pain (27, 
46). Patients who are experiencing pain >50 despite intervention will be asked 
to reschedule testing. If needed, the patient will be referred to their MD for 
standard of care pain control measures. Painful neuropathy will be defined as 
pain scale >10.
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The NPQ was initially validated in 528 chronic pain patients from several 
clinics. This test is able to differentiate neuropathic pain patients from non-
neuropathic pain patients. The NPQ may be used for the initial screening of 
neuropathic pain patients. It also has the ability to provide a quantitative 
measure for the descriptors important in the diagnosis and assessment of 
neuropathic pain. Consequently, it can be used for monitoring of neuropathic 
pain treatments and as an outcome measure.  
For additional details: https://www.ncbi.nlm.nih.gov/pubmed/12966256
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contact; but strong pigmentation spots, tattoos, and moles will be avoided.  

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 Patients will be reminded that if pain becomes too difficult for them to tolerate, 
they can stop the testing at any time.
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-Aδ fiber protocol: 60-millisecond duration, 980-nm stimuli, 1-mm diameter 
stimuli 
-C fiber protocol: 2-second duration, 980-nm stimuli, 5-mm diameter stimuli  
6) 6WLPXODWLRQZLOOEHJLQDWP$FXUUHQWLIVHQVDWLRQLVIHOWDWP$JR
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VXEMHFWLGHQWLILHVWKHVWLPXODWLRQDVSDLQIXOThe current will be increased up to a 
maximum of 1650 mA for the C-fiber protocol and to a maximum of 3500 mA for 
the Aδ-fiber protocol. In rare cases, patients may have pain thresholds that exceed 
the maximum skin temperature considered safe. For these patients, we will use the 
maximum safe stimulus level (3500 mA for the Aδ fiber, 1650 mA for the C 
fiber) to calculate the Aδ:C ratio. For subsequent runs, start at the highest level 
that do not evoke sensation from prior run (LIVHQVDWLRQLVIHOWDWWKDWOHYHOJR
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7) The pain threshold will be obtained using the “method of levels”, using a series of 
ascending stimulation from energy that does not evoke sensation (600mA) and 
increasing by steps of 100mA until the last sensation is recorded as a 30-40 on the 
0-100 pain scale. (0= no sensation, 10= definite sensation/pain, 100 worst 
imaginable pain). The procedure will be repeated three times and the pain 
threshold will be defined as averaging the readings of the 3 successive 
stimulations. The selected current will be applied 4 times. At this current, we 
expect to produce pain 50% of the time, and no pain 50% of the time.  
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4.5 Prior Validation of the DLss 
 
Laser stimulation, similar to what is being used in the DLss, has been used in pain clinics 

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and research since 1975 as a diagnostic test.  It has been proven to be useful and safe. 
Laser irradiation simultaneously activates both A delta and C fibers and primarily heat 
fibers located in the epidermis (up to 50-150 micron depth)(47-49). 
Diode laser stimulation (the DLss used in this protocol) provides relatively uniform 
heating of skin from 50 to 600 microns deep, allowing for a distinct, singular burning or 
singular pricking pain depending on the laser pulse parameters. Experiments using an 
infrared diode laser conducted in Stanford and another institutions have shown that a 
short and a long laser pulse produces, respectively, a singular pinprick sensation 
(representing A-delta stimulation), and a singular burning pain sensation (representing C 
fiber stimulation) when applied to the dorsal hand skin of healthy subjects and pain 
patients volunteers. These preliminary results show that diode laser stimulation can safely 
and selectively activate A delta and C thermos-nociceptors(20, 22, 23, 50). 
Diode lasers similar to the oneused in this study are FDA approved and are often used in 
cosmetic medical procedures for hair removal.The lasers used for cosmetic procedures 
are set at ten times the power density of that used in our study.  
Over 115 subjects have been tested with the DLss. No patient has withdrawn from DLss 
testing due to pain. Two patients had pin-tip sized skin discolorations that resolved in the 
course of a week. 
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There is a remote risk of skin injury or burning by laser stimulation when used for pain 
testing, that occurs by overheating of skin surface. This laser irradiation penetrates the 
skin fairly deeply, and does not allow overheating of the skin’s surface. We also use a 
short, concentrated pulse; this will activate nerve fiber but is not long enough in duration 
to cause tissue damage. We have defined pain threshold levels for testing as moderate 
only, and are therefore only exposing subjects to the minimal stimulation that causes 
brief, moderate pain.  
 
Over 115 subjects have been tested with the DLss. No patient has withdrawn from DLss 
testing due to pain. Two patients had pin-tip sized skin discolorations that resolved in the 
course of a week. 
 
If any patient experiences an adverse event related to testing that is concerning to the 
study staff, protocol director, or PI; or is previously undescribed, we will report this to the 
IRB and SRC. 
 
In addition, this protocol will be monitored by the Stanford DSMC.  
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The primary outcome measure of this study is the difference in the “Aδ:C pain threshold 
ratio” for patients with a painless response to chemotherapy versus painful neuropathy, as 
measured using the DLss. 
 
The “Aδ:C pain threshold ratio” is calculated using the Aδ-fiber and C-fiber pain 
thresholds determined using the protocol outlined in section 4.4. 
 
Each patient will have 2 testing sessions:  
1)
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This is not a safety outcome. 
 
5.1.2    Outcome Measure for Aim 2 
The second outcome measure of this study is the correlation between the “Aδ:C pain 
threshold ratio” and the development of pain. 
 
We will generate a Spearman correlation coefficient for the “Aδ:C pain threshold ratio” 
obtained at the first testing session and the presence or absence of pain at the time of the 
second test.  
 
This is not a safety outcome. 
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The Aδ:C pain threshold ratio will be recorded for each eligible and evaluable patient for 
both time points. We will calculate the average value of this parameter for each group (A 
and B) on a logarithmic scale. Then we will use a standard statistical two side t-test to 
compare the “Aδ:C pain threshold ratio” in the painless CIPN group to the painful CIPN 
group. We hypothesize that the painful CIPN group will have statistically significantly 
higher value “Aδ:C pain threshold ratio” than those without. 
To assess whether the “Aδ:C pain threshold ratio” predicts future painful or painless 
CIPN, we will conduct logistic regression analysis of the binary pain value (pain or no 
pain) at the time of the second testing (independent variable) on the “Aδ:C pain threshold 
ratio” at the time of the first testing (dependent variable). It will allow us to estimate 
whether the “Aδ:C pain threshold ratio” predicts the chances of a patient to develop pain. 
As an exploratory analysis, we will explore if the “Aδ:C pain threshold ratio” obtained at 

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the first testing session predicts an increase in the numeric pain scale at the second testing 
session. 
 
5.3 
Sample size 
The power analysis of the preliminary data presented here was conducted by Alex 
McMillan (Stanford). The analysis was done on the natural logarithm scale and converted 
back using anti-logarithms. The geometric mean (GM) ratio of chemotherapy was 1.58 
times the GM for healthy group. The GM in the diabetic group was 1.38 times the GM of 
the healthy group. The most variable group (Diabetics) had a standard deviation (log 
scale) of 0.33 and this value was used for sample size calculations. 
These calculations showed that sample size of 25 subjects in each group will have 80% 
power to detect a 1.31 fold Aδ:C pain threshold ratio in patients with painful versus 
painless CIPN. Based on the analysis of our preliminary data, we expect the effect size to 
be larger than 1.31. 
It is possible that we will have more patients accrued to Group B compared to Group A 
because uncomfortable patients may not want to participate in as great a number. In this 
case, we will consider use using an “unbalanced” (“non-symmetrical”) statistical design, 
i.e. a design with unequal number of subjects in the two groups. If we get fewer than 25 
patients with pain we will increase the number of patients in the group without pain to 
preserve the power of 80% in order to detect the effect size. If this approach is necessary, 
we will apply for a no-cost extension of the NIH SBIR. 
Table 5.1 shows several possible combinations of sample sizes which will assure the 
power 80% to detect the effect size 1.31. The sample sizes were calculated using SAS 
9.14 software, procedure proc power. The calculations are based on the use of a t-test on 
the natural logarithm scale with a standard deviation of 0.33, detectable effect size 0.24 
on the log scale. 
Scenario 
Subjects with pain 
Subjects without pain 
1 
25 
25 
2 
24 
26 
3 
23 
27 
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22 
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5 
21 
29 
6 
20 
31 
7 
19 
34 
8 
18 
37 
9 
17 
42 
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Based on the new patient volume in the women’s cancer center, we expect to recruit 50 
patients in 12 months. However, should the study require a non-symmetric statistical 

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method and its clear we will not be able to recruit 59 patients (scenario 9), we will we 
will request a12 month no-cost extension from the NIH/NCI.
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Subject #__________________ 
Neuropathic Pain Questionnaire 
 
In order to assess and treat your pain problem, we need to thoroughly understand just 
exactly what type of pain you have, and how it may or may not change over time. You 
may have only one site of pain, or you may have more than one. 
 
Please name the site of pain which is most severe or disturbing for you (eg, arm, foot, etc.) 
 
_____________________________________________________________________ 
 
_____________________________________________________________________ 
 
For all of the following questions, please rate your pain at the site you just listed. Please 
use the space below to describe your pain in your own words: 
 
_______________________________________________________________________ 
 
_______________________________________________________________________ 
 
Please use the items below to rate your pain as it usually feels. Indicate a number which 
represents your pain on each scale. For example, if you have no burning pain, you would 
rate the first item “0”. If you have the worst burning pain imaginable, you would rate it 
“100”. If neither of those fits your pain because it is in between, choose a number which 
fits your pain. 
 
1. Burning Pain 
0 
 
 
 
100 
 
Please rate your usual pain: ______ 
No Burning Pain 
 
Worst Burning Pain Imaginable 
 
 
 
 
 
2. Overly Sensitive to Touch 
0 
 
 
 
100 
 
Please rate your usual pain: ______ 
No Oversensitivity  
Worst Oversensitivity Imaginable 
 
 
 
 
3. Shooting Pain 
0 
 
 
 
100 
 
Please rate your usual pain: ______ 
No Shooting Pain  
Worst Shooting Pain Imaginable 
 
 
 
 
4. Numbness 
0 
 
 
 
100 
 
Please rate your usual pain: ______ 
No Numbness 
 
Worst Numbness Imaginable 
 
5. Electric Pain 
0 
 
 
 
100 
 
Please rate your usual pain: ______ 
No Electric Pain 
 
Worst Electric Pain Imaginable 
 

Subject #__________________ 
 
6. Tingling Pain 
0 
 
 
 
100 
 
Please rate your usual pain: ______ 
No Tingling Pain 
 
Worst Tingling Pain Imaginable 
 
 
7. Squeezing Pain 
0 
 
 
 
100 
 
Please rate your usual pain: ______ 
No Squeezing Pain  
Worst Squeezing Pain Imaginable 
 
 
8. Freezing Pain 
0 
 
 
 
100 
 
Please rate your usual pain: ______ 
No Freezing Pain  
Worst Freezing Pain Imaginable 
 
 
9. How unpleasant is your usual pain? 
0 
 
 
 
100 
 
Please rate your usual pain: ______ 
Not Unpleasant at All 
 
Most Unpleasant Imaginable 
 
 
10. How Overwhelming is your usual pain? 
0 
 
 
 
100 
 
Please rate your usual pain: ______ 
Not Overwhelming  at All 
 
Worst Overwhelming  
Pain Imaginable 
 
 
 
 
 
 
We are also interested in learning what circumstances cause changes in your pain. Please 
write the number that indicates the amount you experience each of the following: 
 
11. Increased pain due to touch 
0 
 
 
 
100 
 
Please rate your usual pain: ______ 
No Increase at All  
Greatest Increase Imaginable 
 
 
12. Increased pain due to weather changes 
0 
 
 
 
100 
 
Please rate your usual pain: ______ 
No Increase at All  
Greatest Increase Imaginable